https://www.cazypedia.org/api.php?action=feedcontributions&user=Stefan+Janecek&feedformat=atomCAZypedia - User contributions [en-ca]2024-03-29T01:26:19ZUser contributionsMediaWiki 1.35.10https://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=17901User:Stefan Janecek2024-02-12T19:23:19Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as families [[GH57]] with [[GH119]], and eventually also [[GH126]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve fifteen [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]], [[CBM69]], [[CBM74]], [[CBM82]] and [[CBM83]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs]; for the most recent one, being held in autumn 2022, please click: [http://imb.savba.sk/~janecek/Alamys/Alamy_8/ ALAMY_8].<br />
<br />
He serves as the Associate Editor of the journal [http://www.springer.com/chemistry/biotechnology/journal/13205 3Biotech] and Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology, too.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17900Glycoside Hydrolase Family 1192024-02-12T19:20:52Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family [[GH57]] (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|400px|right|'''Figure 1. Original structure comparison of families [[GH57]] and GH119 <cite>Janecek2012</cite>.''' (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.]]<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a specificity very similar to that of IgtZ: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57 <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been shown that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of [[GH57]], namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt the (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices also adopted by [[GH57]] <cite>Janecek2012,Polacek2023</cite>. Based on these differential features, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, sequence comparisons indicate that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|400px|right|'''Figure 2. Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>.''' Tree branches in the same clade share the same colour. Stars mark experimentally characterized sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name colored by phylum and predicted sequence domain composition.]]<br />
<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe ''et al.'' <cite>Watanabe2006</cite>, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and [[GH57]] MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17896Glycoside Hydrolase Family 1192024-02-11T15:44:12Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family [[GH57]] (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|400px|right|'''Figure 1. Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>.''' (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.]]<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57 <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of [[GH57]], namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, [[GH13]], which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in [[GH70]] and [[GH77]], all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|400px|right|'''Figure 2. Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>.''' Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.]]<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe ''et al.'' <cite>Watanabe2006</cite>, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and [[GH57]] MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17895Glycoside Hydrolase Family 1192024-02-11T15:43:35Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratoApproved}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family [[GH57]] (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|400px|right|'''Figure 1. Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>.''' (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.]]<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57 <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of [[GH57]], namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, [[GH13]], which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in [[GH70]] and [[GH77]], all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|400px|right|'''Figure 2. Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>.''' Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.]]<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe ''et al.'' <cite>Watanabe2006</cite>, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and [[GH57]] MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17890Glycoside Hydrolase Family 1192024-02-09T11:43:25Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|400px|right|'''Figure 1. Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>.''' (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.]]<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and [[57]] <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, [[GH13]], which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in [[GH70]] and [[GH77]], all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|400px|right|'''Figure 2. Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>.''' Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.]]<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe ''et al.'' <cite>Watanabe2006</cite>, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and [[GH57]] MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17889Glycoside Hydrolase Family 1192024-02-09T11:41:44Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|]]'''Figure 1. Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.'''<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and [[57]] <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, [[GH13]], which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in [[GH70]] and [[GH77]], all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|'''Figure 2. Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.]]<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe ''et al.'' <cite>Watanabe2006</cite>, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and [[GH57]] MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17888Glycoside Hydrolase Family 1192024-02-09T11:40:16Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|]]'''Figure 1. Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.'''<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and [[57]] <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, [[GH13]], which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in [[GH70]] and [[GH77]], all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|]]'''Figure 2. Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.'''<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe ''et al.'' <cite>Watanabe2006</cite>, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and [[GH57]] MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17887Glycoside Hydrolase Family 1192024-02-09T11:34:36Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|]]'''Figure 1.''' Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and [[57]] <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, [[GH13]], which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in [[GH70]] and [[GH77]], all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|]]'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe ''et al.'' <cite>Watanabe2006</cite>, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and [[GH57]] MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17886Glycoside Hydrolase Family 1192024-02-09T11:32:28Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|]]'''Figure 1.''' Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and [[57]] <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, [[GH13]], which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in [[GH70]] and [[GH77]], all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|]]'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ <cite>Watanabe2006</cite>.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17885Glycoside Hydrolase Family 1192024-02-09T11:30:55Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|]]'''Figure 1.''' Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57 <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, GH13, which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in GH70 and GH77, all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|]]'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ <cite>Watanabe2006</cite>.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17884Glycoside Hydrolase Family 1192024-02-09T11:30:27Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|'''Figure 1.''' Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57 <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, GH13, which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in GH70 and GH77, all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], CBM25 and CBM26, fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal CBM25 <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|]]'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ <cite>Watanabe2006</cite>.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17883Glycoside Hydrolase Family 1192024-02-09T11:28:11Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in [[GH13]] <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|'''Figure 1.''' Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: [{{PDBlink}}1K1Y 1K1Y]; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.<br />
<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57 <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, GH13, which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in GH70 and GH77, all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], [[CBM25]] and [[CBM26]], fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal [[CBM25]] <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ <cite>Watanabe2006</cite>.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17882Glycoside Hydrolase Family 1192024-02-09T11:25:14Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in GH13 <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|'''Figure 1.''' Original structure comparison of families [[GH57]] and GH119 from 2012 <cite>Janecek2012</cite>. (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' [[GH57]] 4-α-glucanotransferase (red; PDB: 1K1Y; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in [[GH57]] 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with [[GH57]] 4-α-glucanotransferase is also shown.<br />
Vuillemin ''et al.'' <cite>Vuillemin2024</cite> expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119. They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' <cite>Watanabe2006</cite> confirmed by polarimetry in 2006. The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57 <cite>Janecek2012,Polacek2023</cite>. Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and [[GH57]] crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of [[GH57]] <cite>Janecek2012</cite>. The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base <cite>Imamura2001,Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity <cite>Vuillemin2024</cite>. Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices <cite>Janecek2012,Polacek2023</cite>.<br />
These characteristics differentiate the amylolytic families [[GH57]] and GH119 from the main α-amylase family, GH13, which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in GH70 and GH77, all of which are members of clan GH-H <cite>Janecek2022</cite>. Based on these differences, GH119 and [[GH57]] define clan GH-S <cite>Vuillemin2024</cite>.<br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families [[CBM20]], [[CBM25]] and [[CBM26]], fibronectin type III (FN-III) and dockerin domains, among others <cite>Polacek2023, Vuillemin2024,Janecek2019</cite>. A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns <cite>Vuillemin2024</cite>. Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two [[CBM20]] in tandem and a C-terminal [[CBM25]] <cite>Polacek2023</cite>.<br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences <cite>Vuillemin2024</cite>. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition.<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ <cite>Watanabe2006</cite>.<br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs <cite>Janecek2012,Polacek2023</cite>. The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis <cite>Vuillemin2024</cite>.<br />
;First general acid/base residue identification: As above, also inferred through alignment <cite>Janecek2012,Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119) <cite>#Vuillemin2024</cite>.<br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
#Blesak2012 pmid=22527043<br />
#Vuillemin2024 pmid=38280706<br />
#Imamura2001 pmid=11591160<br />
#Imamura2003 pmid=12618437<br />
#Janecek2019 pmid=31536775<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17881Glycoside Hydrolase Family 1192024-02-09T11:15:38Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' <cite>Watanabe2006</cite> expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase <cite>Watanabe2006</cite>.<br />
<br />
In the CAZy database, the two largest amylolytic families, [[GH13]] and [[GH57]], are notably multi-specific, with α-amylase representing just one of more than 30 specificities in GH13 <cite>Janecek2022</cite>. Family GH119 was predicted in 2012 <cite>Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity <cite>Polacek2023</cite>. This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families [[GH57]] and GH119 <cite>Janecek2011,Blesak2012</cite>.<br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|'''Figure 1.''' Original structure comparison of families GH57 and GH119 from 2012.[3] (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' GH57 4-α-glucanotransferase (red; PDB: 1K1Y; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in GH57 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with GH57 4-α-glucanotransferase is also shown.<cite>#Janecek2012</cite>]]<br />
Vuillemin ''et al.'' expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119.<cite>#Vuillemin2024</cite> They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase.<cite>#Vuillemin2024</cite><br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' confirmed by polarimetry in 2006.<cite>Watanabe2006</cite> The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57.<cite>#Janecek2012</cite><cite>#Polacek2023</cite> Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and GH57 crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of GH57.<cite>#Janecek2012</cite> The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base<cite>#Imamura2001</cite><cite>#Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity.<cite>#Vuillemin2024</cite> Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices.<cite>#Janecek2012</cite><cite>#Polacek2023</cite><br />
These characteristics differentiate the amylolytic families GH57 and GH119 from the main α-amylase family, GH13, which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in GH70 and GH77, all of which are members of clan GH-H.<cite>Janecek2022</cite> Based on these differences, GH119 and GH57 define clan GH-S.<cite>#Vuillemin2024</cite><br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families 20, 25 and 26, fibronectin type III (FN-III) and dockerin domains, among others.<cite>Polacek2023</cite><cite>#Vuillemin2024</cite><cite>#Janecek2019</cite> A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns.<cite>#Vuillemin2024</cite> Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two CBM20 in tandem and a C-terminal CBM25.<cite>#Polacek2023</cite><br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition..<cite>#Vuillemin2024</cite>]]<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<cite>Watanabe2006</cite><br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs.<cite>#Janecek2012</cite><cite>#Polacek2023</cite> The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis.<cite>#Vuillemin2024</cite><br />
;First general acid/base residue identification: As above, also inferred through alignment<cite>#Janecek2012</cite><cite>#Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119).<cite>#Vuillemin2024</cite><br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
<br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
<br />
#Blesak2012 pmid=22527043<br />
<br />
#Vuillemin2024 pmid=38280706<br />
<br />
#Imamura2001 pmid=11591160<br />
<br />
#Imamura2003 pmid=12618437<br />
<br />
#Janecek2019 pmid=31536775<br />
<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17880Glycoside Hydrolase Family 1192024-02-09T11:07:25Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. <cite>Watanabe2006</cite> This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase.<cite>Watanabe2006</cite><br />
<br />
In the CAZy database, the two largest amylolytic families, GH13 and GH57, are notably multi-specific, with α-amylase representing just one of more than 30 specificities in GH13.<cite>Janecek2022</cite> Family GH119 was predicted in 2012<cite>#Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity.<cite>#Polacek2023</cite> This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families GH57 and GH119.<cite>#Janecek2011</cite><cite>#Blesak2012</cite><br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|'''Figure 1.''' Original structure comparison of families GH57 and GH119 from 2012.[3] (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' GH57 4-α-glucanotransferase (red; PDB: 1K1Y; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in GH57 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with GH57 4-α-glucanotransferase is also shown.<cite>#Janecek2012</cite>]]<br />
Vuillemin ''et al.'' expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119.<cite>#Vuillemin2024</cite> They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase.<cite>#Vuillemin2024</cite><br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' confirmed by polarimetry in 2006.<cite>Watanabe2006</cite> The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57.<cite>#Janecek2012</cite><cite>#Polacek2023</cite> Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and GH57 crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of GH57.<cite>#Janecek2012</cite> The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base<cite>#Imamura2001</cite><cite>#Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity.<cite>#Vuillemin2024</cite> Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices.<cite>#Janecek2012</cite><cite>#Polacek2023</cite><br />
These characteristics differentiate the amylolytic families GH57 and GH119 from the main α-amylase family, GH13, which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in GH70 and GH77, all of which are members of clan GH-H.<cite>Janecek2022</cite> Based on these differences, GH119 and GH57 define clan GH-S.<cite>#Vuillemin2024</cite><br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families 20, 25 and 26, fibronectin type III (FN-III) and dockerin domains, among others.<cite>Polacek2023</cite><cite>#Vuillemin2024</cite><cite>#Janecek2019</cite> A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns.<cite>#Vuillemin2024</cite> Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two CBM20 in tandem and a C-terminal CBM25.<cite>#Polacek2023</cite><br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition..<cite>#Vuillemin2024</cite>]]<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<cite>Watanabe2006</cite><br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs.<cite>#Janecek2012</cite><cite>#Polacek2023</cite> The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis.<cite>#Vuillemin2024</cite><br />
;First general acid/base residue identification: As above, also inferred through alignment<cite>#Janecek2012</cite><cite>#Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119).<cite>#Vuillemin2024</cite><br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
<br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
<br />
#Blesak2012 pmid=22527043<br />
<br />
#Vuillemin2024 pmid=38280706<br />
<br />
#Imamura2001 pmid=11591160<br />
<br />
#Imamura2003 pmid=12618437<br />
<br />
#Janecek2019 pmid=31536775<br />
<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_119&diff=17879Glycoside Hydrolase Family 1192024-02-09T11:04:13Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]: [[User:Eduardo Moreno Prieto|Eduardo Moreno Prieto]]<br />
* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]] and [[User:Bernard Henrissat|Bernard Henrissat]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH119'''<br />
|-<br />
|'''Clan''' <br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known (inferred)<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH119.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
<br />
== Substrate specificities ==<br />
Glycoside hydrolase family 119 (GH119) contains a relatively small number of exclusively bacterial sequences. The first experimentally-characterized member was the amylolytic enzyme IgtZ from ''Niallia circulans'' AM7 (formerly ''Bacillus circulans''). Watanabe ''et al.'' expressed IgtZ’s full sequence and assayed it against a range of oligo- and polymeric α-glucans, demonstrating its ability to break down amylose and soluble starch but not pullulan or dextran. <cite>Watanabe2006</cite> This suggests a strict specificity towards α-1,4 over α-1,6-glucan bonds. The enzyme also acts on maltooligosaccharides with a minimum degree of polymerization (DP) of 4 and maltooligosyl trehaloses with maltooligosaccharide portions of at least 4 monosaccharide units. The enzyme hydrolytic action yields primarily disaccharides (maltose or trehalose) accompanied by smaller amounts of glucose and other maltodextrins. The enzyme specificity increases with the DP of the substrate. Based on these findings, the authors categorized IgtZ as an α-amylase.<cite>Watanabe2006</cite><br />
<br />
In the CAZy database, the two largest amylolytic families, GH13 and GH57, are notably multi-specific, with α-amylase representing just one of more than 30 specificities in GH13.<cite>Janecek2022</cite> Family GH119 was predicted in 2012<cite>#Janecek2012</cite> to share its catalytic domain fold and catalytic machinery with those of the family GH57 (Fig. 1). It had been also predicted that GH119 would be largely mono-specific, with α-amylase being the primary specificity.<cite>#Polacek2023</cite> This was based on the composition of one of its conserved sequence regions (CSRs), specifically CSR-5, which correlates with substrate specificity in families GH57 and GH119.<cite>#Janecek2011</cite><cite>#Blesak2012</cite><br />
[[File:GH57 GH119 structure comparison.jpg|thumb|300px|right|'''Figure 1.''' Original structure comparison of families GH57 and GH119 from 2012.[3] (a) Catalytic (β/α)<sub>7</sub>-barrel with succeeding α-helical bundle of ''Thermococcus litoralis'' GH57 4-α-glucanotransferase (red; PDB: 1K1Y; residues M1-Q381) superimposed with substantial part of the (β/α)<sub>7</sub>-barrel domain of ''Niallia circulans'' GH119 α-amylase IgtZ (blue; model; residues T121-D429). The rectangle indicates a detailed view on the right. (b) Focus on catalytic residues in GH57 4-α-glucanotransferase (Glu123 and Asp214) and the predicted catalytic machinery in GH119 α-amylase (Glu231 and Asp373). Acarbose occupying subsites -1 through +3 from the complex with GH57 4-α-glucanotransferase is also shown.<cite>#Janecek2012</cite>]]<br />
Vuillemin ''et al.'' expressed recombinantly the core domain of five other GH119 sequences representing the major phylogenetic clades of family GH119.<cite>#Vuillemin2024</cite> They all showed a very similar specificity as IgtZ’s: activity on glycogen, soluble starch, amylose and maltooligosaccharides with minimum DP5, but not on pullulan or dextran. This result confirmed the ''in silico'' prediction of uniform specificity. Their product profiles were also similar to IgtZ’s, except for that of α-amylase CocoGH119 from ''Corallococcus coralloides'' DSM 2259, which only produced DP2 and DP3 maltooligosaccharides from longer-chain substrates. This suggests that this enzyme is a maltogenic α-amylase.<cite>#Vuillemin2024</cite><br />
<br />
== Kinetics and Mechanism ==<br />
''Niallia circulans'' IgtZ is a retaining enzyme as Watanabe ''et al.'' confirmed by polarimetry in 2006.<cite>Watanabe2006</cite> The authors did not discuss the enzyme’s possible exo- or endo-acting mode of action.<br />
<br />
== Catalytic Residues ==<br />
''In silico'' studies have revealed a close phylogenetic relationship between GH families 119 and 57.<cite>#Janecek2012</cite><cite>#Polacek2023</cite> Through multiple sequence alignment (MSA) and superimposition of GH119 homology models and GH57 crystallographic structures, it has been demonstrated that GH119 sequences share the same five CSRs typical of GH57.<cite>#Janecek2012</cite> The strictly conserved, catalytic residues of GH57, namely a strand β4 glutamate serving as nucleophile and a β7 aspartate serving as acid/base<cite>#Imamura2001</cite><cite>#Imamura2003</cite> are located in CSR-3 and CSR-4, respectively. The equivalent residues in CocoGH119 (E225 and D369) have been found to be essential to catalysis by site-directed mutagenesis experiments resulting in complete abolishment of the enzyme’s activity.<cite>#Vuillemin2024</cite> Furthermore, homology models of GH119 sequences suggest that their putative catalytic domain may adopt a (β/α)<sub>7</sub>-barrel (i.e., an incomplete TIM-barrel) fold followed by a bundle of α-helices.<cite>#Janecek2012</cite><cite>#Polacek2023</cite><br />
These characteristics differentiate the amylolytic families GH57 and GH119 from the main α-amylase family, GH13, which adopts a (β/α)<sub>8</sub>-barrel fold (i.e., a classical TIM-barrel) and has a Asp-Glu-Asp catalytic triad, as also observed in GH70 and GH77, all of which are members of clan GH-H.<cite>Janecek</cite> Based on these differences, GH119 and GH57 define clan GH-S.<cite>#Vuillemin2024</cite><br />
== Three-dimensional structures ==<br />
No 3D structure of a GH119 protein has been experimentally established so far. However, domain prediction indicates that several GH119 proteins exhibit a multi-modular architecture consisting of an N-terminal, putatively-catalytic, main domain followed by a variable number of additional domains, including carbohydrate-binding modules (CBM) of families 20, 25 and 26, fibronectin type III (FN-III) and dockerin domains, among others.<cite>Polacek2023</cite><cite>#Vuillemin2024</cite><cite>#Janecek2019</cite> A phylogenetic tree of the family annotated with predicted domain architecture (Fig. 2) shows that different branches exhibit distinctive auxiliary domain patterns.<cite>#Vuillemin2024</cite> Domain prediction for IgtZ suggests that this enzyme comprises an N-terminal, putative catalytic domain, followed by an FN-III, two CBM20 in tandem and a C-terminal CBM25.<cite>#Polacek2023</cite><br />
[[File:GH119_phylogenetic_tree.jpg|thumb|300px|right|'''Figure 2.''' Phylogenetic tree representing 52 GH119 representative sequences. Tree branches in the same clade share the same colour. Stars mark experimentally characterised sequences. The remaining annotations to each branch, from left to right, include: NCBI accession number, source organism name coloured by phylum and predicted sequence domain composition..<cite>#Vuillemin2024</cite>]]<br />
== Family Firsts ==<br />
;First stereochemistry determination:The first evidence of a retaining mechanism within the family was presented by Watanabe and colleagues, who conducted a polarimetry study of the maltooligosaccharide products resulting from the hydrolysis of maltopentaosyl trehalose by IgtZ.<cite>Watanabe2006</cite><br />
;First catalytic nucleophile identification: Inferred to be a strictly conserved, strand β4 glutamate located in the CSR-3 of GH119 and GH57 MSAs.<cite>#Janecek2012</cite><cite>#Polacek2023</cite> The equivalent residue in CocoGH119 (E225) is essential to catalysis as demonstrated through site-directed mutagenesis.<cite>#Vuillemin2024</cite><br />
;First general acid/base residue identification: As above, also inferred through alignment<cite>#Janecek2012</cite><cite>#Polacek2023</cite> and confirmed by site-directed mutagenesis to be a fully conserved, β7 aspartate located in CSR-4 of the family (D369 in CocoGH119).<cite>#Vuillemin2024</cite><br />
;First 3-D structure: Not yet determined.<br />
<br />
== References ==<br />
<biblio><br />
<br />
#Watanabe2006 pmid=17090949<br />
#Janecek2022 Janeček Š and Svensson B (2022) ''How many α-amylase GH families are there in the CAZy database? Amylase''. 6:1–10. [https://doi.org/10.1515/amylase-2022-0001 DOI:10.1515/amylase-2022-0001]<br />
<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polaček A and Janeček Š (2023). ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57. Biologia''. 78:1847–1860. [https://doi.org/10.1007/s11756-023-01349-y DOI:10.1007/s11756-023-01349-y]<br />
#Janecek2011 pmid=21786160<br />
<br />
#Blesak2012 pmid=22527043<br />
<br />
#Vuillemin2024 pmid=38280706<br />
<br />
#Imamura2001 pmid=11591160<br />
<br />
#Imamura2003 pmid=12618437<br />
<br />
#Janecek2019 pmid=31536775<br />
<br />
</biblio><br />
<br />
<!-- Do not delete this Category tag --><br />
[[Category:Glycoside Hydrolase Families|GH119]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_57&diff=17809Glycoside Hydrolase Family 572024-02-05T11:37:26Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
* [[Responsible Curator]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}}<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH57'''<br />
|-<br />
|'''Clan'''<br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH57.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Substrate specificities ==<br />
[[Glycoside hydrolase]] family 57 was established in 1996 <cite>Henrissat1996</cite> based on the existence of the sequences of two “α-amylases” that were dissimilar to typical family [[GH13]] α-amylases <cite>MacGregor2001</cite>. The two were the heat-stable eubacterial amylase from ''Dictyoglomus thermophilum'' known from 1988 <cite>Fukusumi1988</cite> and the extremely thermostable archaeal amylase from ''Pyrococcus furiosus'' determined in 1993 <cite>Laderman1993a</cite>.<br />
<br />
The family has expanded mainly due to the results of genome sequencing projects. More than a thousand of members are known <cite>Cantarel2009,Lombard2014</cite>, all from prokaryotes (with ~1:4 ratio for Archaea:Bacteria) <cite>Blesak2012</cite>. The enzyme specificities of family GH57 includes α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]), α-galactosidase (EC [{{EClink}}3.2.1.22 3.2.1.22]), amylopullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]), branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]) and 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]).<br />
<br />
An archaeal GH57 amylopullulanase from ''Staphylothermus marinus'' has been described exhibiting also the activity of cyclodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]) <cite>Li2013</cite>. Based on a preliminary observation that the PF0870 protein encoded in the ''Pyrococcus furiosus'' genome produced maltose <cite>Comfort2008</cite>, a group of GH57 members with proposed specificity of maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]) was predicted <cite>Blesak2013</cite> together with another group of non-specified amylases following the partial characterization of an amylolytic enzyme from an uncultured bacterium <cite>Wang2011</cite>. The maltogenic specificity (or maltose-forming amylase) has already been definitively confirmed by both biochemical <cite>Jung2014,Jeon2014</cite> and structural <cite>Park2014</cite> studies. The family GH57 contains further a group of probably non-enzymatic members, i.e. the so-called α-amylase-like proteins having a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
<br />
It is worth mentioning that the two founding members, i.e. the “α-amylases” from ''Dictyoglomus thermophilum'' and ''Pyrococcus furiosus'' are 4-α-glucanotransferases; the former was proven to have transglycosylating activity <cite>Nakajima2004</cite>, whereas the latter was already known to exhibit also the 4-α-glucanotransferase activity <cite>Laderman1993b</cite>.<br />
<br />
A detailed in silico prediction study has indicated a close relatedness of family GH57 to the family GH119 concerning catalytic domain fold, catalytic machinery and conserved sequence regions <cite>Janecek2012</cite>. This original prediction has recently been updated using the AlphFold-generated structural model of a GH119 representative <cite>Polacek2023</cite> and finally confirmed also experimentally by the biochemical characterization of five GH119 members exhibiting a single α-amylase specificity but distinct product profile <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
A direct evidence for the stereochemical outcome of the enzyme-catalyzed reaction has been presented for the branching enzyme from ''Thermus thermophilus'' <cite>Palomo2011</cite> by the NMR analysis of reaction products. The previous observation of a trapped covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> was also a strong evidence that the GH57 enzymes operate with [[retaining|retention]] of anomeric configuration through a [[classical Koshland retaining mechanism]] with retention of anomeric configuration. The X-ray structure of the 4-α-glucanotransferase from ''Thermococcus litoralis'' revealed average distances of 6.72 Å and 6.97 Å between the [[catalytic nucleophile]] (Glu123) and [[general acid/base]] (Asp214) in the free and acarbose-bound forms of the enzyme, respectively, which also supports a retaining mechanism for this family <cite>Imamura2003</cite> (see also <cite>Davies1995</cite>).<br />
<br />
Detailed kinetic studies have been performed on several GH57 enzymes, including the 4-α-glucanotransferases from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> and ''Pyrococcus furiosus'' <cite>Tang2006</cite>, amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>, and branching enzymes from ''Thermococcus kodakaraensis'' <cite>Murakami2006</cite> and ''Thermus thermophilus'' <cite>Palomo2011</cite>.<br />
<br />
== Catalytic Residues ==<br />
The sequences of GH57 members are very diverse. Some sequences are shorter than 400 residues whereas others are longer than 1,500 residues <cite>Janecek2005</cite>. This complicated early efforts to align the GH57 sequences using standard alignment methods. A detailed bioinformatics study by Zona ''et al.'' <cite>Zona2004</cite> focused on all available GH57 sequences at that time and identified five conserved sequence regions. This study used knowledge of the identity of the [[catalytic nucleophile]] (Glu123) in the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001</cite> together with the three-dimensional structure <cite>Imamura2003</cite> (PDB ID [{{PDBlink}}1k1w 1k1w]) that revealed the [[general acid/base]] residue (Asp214).<br />
<br />
The [[catalytic nucleophile]] (a glutamate) and [[general acid/base]] (an aspartate) are located in the conserved sequence regions 3 and 4, respectively. In addition to assignments in ''Thermococcus litoralis'' 4-α-glucanotransferase discussed above, these residues were identified in the amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>. The [[catalytic nucleophile]] was also identified in the α-galactosidase from ''Pyrococcus furiosus'' although no success was achieved in assigning the [[general acid/base]] <cite>vanLieshout2003</cite>. It should be taken into account that some GH57 members, which are only hypothetical enzymes/proteins without any biochemical characterization, may lack one or even both catalytic residues <cite>Zona2004,Janecek2011</cite>.<br />
<br />
Based on the five identified conserved sequence regions, the residues His13, Glu79, Glu216 and Asp354 together with Trp120, Trp221 and Trp357 (''Thermococcus hydrothermalis'' amylopullulanase numbering) were postulated <cite>Zona2004</cite> as important determinants of the individual GH57 enzyme specificities <cite>Janecek2011,Blesak2012,Blesak2013</cite>. Of these, the Trp221 has already been confirmed to contribute to the transglycosylation activity of 4-α-glucanotransferase since the mutant W229H of the enzyme from ''Pyrococcus furiosus'' exhibited markedly decreased transglycosylation activity in comparison with the wild-type counterpart <cite>Tang2006</cite>.<br />
<br />
== Three-dimensional structures ==<br />
The structure of the catalytic domain adopts a (β/α)7-barrel, i.e. the irregular (β/α)8-barrel called a pseudo TIM-barrel. In the case of the ''Thermococcus litoralis'' 4-α-glucanotransferase <cite>Imamura2003</cite> the catalytic domain is succeeded by a C-terminal non-catalytic domain consisting of only β-strands that adopts a twisted β-sandwich fold. In the three-dimensional structure of the α-amylase AmyC from ''Thermotoga maritima'' <cite>Dickmanns2006</cite> (PDB ID [{{PDBlink}}2b5d 2b5d]) (note that the sequence of this enzyme strongly resemles that of a branching enzyme <cite>Blesak2012</cite>), the corresponding catalytic (β/α)7-barrel is followed by a five-helix domain C, a small helical domain B being protruded out of the catalytic pseudo TIM barrel in the place of the loop 2 (i.e. succeeding the strand β2). This structure was found to be closely similar to that of the GH57 member of unknown function from ''Thermus thermophilus'' (PDB ID [{{PDBlink}}1ufa 1ufa]). Two structures of biochemically characterized branching enzymes were solved and published: one from ''Thermus thermophilus'' <cite>Palomo2011</cite> (PDB ID [{{PDBlink}}3p0b 3p0b]) and the other one from ''Thermococcus kodakaraensis'' <cite>Santos2011</cite> (PDB ID [{{PDBlink}}3n8t 3n8t]). The former study <cite>Palomo2011</cite>, importantly, is the first report to prove that a retaining mechanism is employed in the family GH57. Also, the 3-D structure is available for the maltogenic (maltose-forming) amylase from ''Pyrococcus'' sp. ST04 <cite>Park2014</cite> (PDB ID [{{PDBlink}}4cmr 4cmr]). In all cases, the catalytic glutamic acid and aspartic acid residues are located near the C-terminal ends of the strands β4 and β7 of the barrel, respectively <cite>Imamura2003,Dickmanns2006</cite>. There was also a crystallization report in 1995 on a probable GH57 amylopullulanase from ''Pyrococcus woesei'' <cite>Knapp1995</cite>, but the detailed crystallographic analysis of this protein has not been published.<br />
<br />
It is clear that the C-terminal domain cannot be present in some GH57 members with shorter amino acid sequences, e.g., in the α-galactosidases containing less than 400 residues <cite>vanLieshout2003</cite>. On the other hand, some other GH57 members, especially the extra-long amylopullulanases with more than 1,300 residues <cite>Erra-Pujada1999</cite> have to contain even additional domains. One of them could be a longer version of a typical surface layer homology (SLH) motif <cite>Lupas1994</cite> that was named as the so-called SLH motif-bearing domain in the amylopullulanase from ''Thermococcus hydrothermalis'' <cite>Erra-Pujada1999</cite>. This domain was found also in the [[GH15]] glucodextranase from ''Arthrobacter globiformis'' <cite>Mizuno2004</cite>. Remarkably, within the family GH57, the presence of this SLH motif-bearing domain is restricted only for amylopullulanases <cite>Zona2005</cite>.<br />
<br />
It is also worth mentioning that, especially prior the first three-dimensional structure of a GH57 member was available, there were some efforts to join the family GH57 with the main α-amylase family [[GH13]], i.e. the present clan [GH-H] consisting of the families [[GH13]], [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>. Those efforts were focused mainly on looking for some remote homology at the sequence level only <cite>Dong1997,Janecek1998</cite>. Although both GH57 and GH-H employ the same retaining reaction mechanism <cite>Imamura2003,Matsuura1984</cite> the independence of the family GH57 with regard to GH-H clan is at present based not only on differences in the catalytic domain, but more importantly, on the differences in the catalytic machineries and conserved sequence regions <cite>Zona2004,Janecek2002</cite>. As far as other GH families are concerned, the family [[GH38]] α-mannosidase from ''Drosophila melanogaster'' <cite>vandenElsen2001</cite> was revealed to share some structural similarities within the catalytic domain with the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> indicating an eventuality of originating from a common ancestor.<br />
<br />
== Family Firsts ==<br />
;First sterochemistry determination: The first direct evidence of the retaining reaction stereochemistry by product analysis has been delivered by 1H-NMR analysis of the product mixture that confirmed the α-anomeric configuration of the α-1,6-glucosidic bond formed after the incubation of ''Thermus thermophilus'' branching enzyme with amylose <cite>Palomo2011</cite>. Previously, family GH57 enzymes have been indicated to be retaining by trapping of a covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> and a 6.7 Å distance between the catalytic nucleophile and acid/base <cite>Imamura2003</cite>, both of which are consistent with a two-step, double-displacement mechanism. <br />
;First amino acid sequence determination: The first amino acid sequence of the family GH57 was that of the heat stable amylase from an anaerobic thermophilic bacterium ''Dictyoglomus thermophilum'' <cite>Fukusumi1988</cite>. This "α-amylase" was later characterized as 4-α-glucanotransferase <cite>Nakajima2004</cite>. In fact, the family contains many α-amylase-like proteins, i.e. those that exhibit a clear sequence homology with α-amylases, but possess a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
;First conserved sequence regions determination: The five sequence stretches characteristic as conserved regions for the family GH57 were first determined by the bioinformatics study by Zona et al. (2004) <cite>Zona2004</cite>.<br />
;First [[catalytic nucleophile]] identification: The catalytic nucleophile was fist identified by Imamura et al. (2001) <cite>Imamura2001</cite> as Glu123 in the 4-α-glucanotransferase from ''Thermococcus litoralis'' using the 3-ketobutylidene-β-2-chloro-4-nitrophenyl maltopentaoside as a donor.<br />
;First [[general acid/base]] residue identification: Asp214 of the 4-α-glucanotransferase from ''Thermococcus litoralis'' as indicated by the X-ray crystallography and supported by site-directed mutagenesis <cite>Imamura2003</cite> since the D214N mutant exhibited a 10,000-fold decrease of specific activity in comparison with the wild-type enzyme.<br />
;First 3-D structure: The first 3-D structure of a GH57 member was that of the 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2003</cite>.<br />
<br />
== References ==<br />
<biblio><br />
#Henrissat1996 pmid=8687420<br />
#MacGregor2001 pmid=11257505<br />
#Fukusumi1988 pmid=2453362<br />
#Laderman1993a pmid=8226990<br />
#Cantarel2009 pmid=18838391<br />
#Lombard2014 pmid=24270786<br />
#Blesak2012 pmid=22527043<br />
#Li2013 pmid=23001056<br />
#Comfort2008 pmid=18156337<br />
#Blesak2013 pmid=24109595<br />
#Wang2011 pmid=21455739<br />
#Jung2014 pmid=23884203<br />
#Jeon2014 pmid=24835094<br />
#Park2014 pmid=24914977<br />
#Janecek2011 pmid=21786160<br />
#Nakajima2004 pmid=15564678<br />
#Laderman1993b pmid=8226989<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polacek A, Janecek S. ''Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57.'' Biologia 2023; 78(7): 1847-60. [https://doi.org/10.1007/s11756-023-01349-y DOI: 10.1007/s11756-023-01349-y]<br />
#Vuillemin2024 pmid=38280706<br />
#Palomo2011 pmid=21097495<br />
#Imamura2003 pmid=12618437<br />
#Imamura2001 pmid=11591160<br />
#Davies1995 pmid=8535779<br />
#Tang2006 pmid=17035108<br />
#Zona2004 pmid=15233783<br />
#Kang2005 pmid=15599521<br />
#Murakami2006 pmid=16885460<br />
#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16): 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])<br />
#vanLieshout2003 van Lieshout JFT, Verhees CH, Ettema TJG, van der Saar S, Imamura H, Matsuzawa H, van der Oost J, de Vos WM. ''Identification and molecular characterization of a novel type of α-galactosidase from Pyrococcus furiosus.'' Biocatal Biotransform 2003; 21(4-5): 243-52. [http://dx.doi.org/10.1080/10242420310001614342 DOI: 10.1080/10242420310001614342])<br />
#Dickmanns2006 pmid=16510973<br />
#Santos2011 pmid=21104698<br />
#Knapp1995 pmid=8749857<br />
#Erra-Pujada1999 pmid=10322035<br />
#Lupas1994 pmid=8113161<br />
#Mizuno2004 pmid=14660574<br />
#Zona2005 Zona R, Janecek S. ''Relationships between SLH motifs from different glycoside hydrolase families.'' Biologia 2005; 60(Suppl. 16): 115-21. ([http://biologia.savba.sk/Suppl_16/Zona_R.pdf PDF])<br />
#Dong1997 pmid=9293009<br />
#Janecek1998 pmid=9721603<br />
#Matsuura1984 pmid=6609921<br />
#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])<br />
#vandenElsen2001 pmid=11406577<br />
</biblio><br />
<br />
[[Category:Glycoside Hydrolase Families|GH057]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_57&diff=17808Glycoside Hydrolase Family 572024-02-05T11:34:51Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
* [[Responsible Curator]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}}<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH57'''<br />
|-<br />
|'''Clan'''<br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH57.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Substrate specificities ==<br />
[[Glycoside hydrolase]] family 57 was established in 1996 <cite>Henrissat1996</cite> based on the existence of the sequences of two “α-amylases” that were dissimilar to typical family [[GH13]] α-amylases <cite>MacGregor2001</cite>. The two were the heat-stable eubacterial amylase from ''Dictyoglomus thermophilum'' known from 1988 <cite>Fukusumi1988</cite> and the extremely thermostable archaeal amylase from ''Pyrococcus furiosus'' determined in 1993 <cite>Laderman1993a</cite>.<br />
<br />
The family has expanded mainly due to the results of genome sequencing projects. More than a thousand of members are known <cite>Cantarel2009,Lombard2014</cite>, all from prokaryotes (with ~1:4 ratio for Archaea:Bacteria) <cite>Blesak2012</cite>. The enzyme specificities of family GH57 includes α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]), α-galactosidase (EC [{{EClink}}3.2.1.22 3.2.1.22]), amylopullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]), branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]) and 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]).<br />
<br />
An archaeal GH57 amylopullulanase from ''Staphylothermus marinus'' has been described exhibiting also the activity of cyclodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]) <cite>Li2013</cite>. Based on a preliminary observation that the PF0870 protein encoded in the ''Pyrococcus furiosus'' genome produced maltose <cite>Comfort2008</cite>, a group of GH57 members with proposed specificity of maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]) was predicted <cite>Blesak2013</cite> together with another group of non-specified amylases following the partial characterization of an amylolytic enzyme from an uncultured bacterium <cite>Wang2011</cite>. The maltogenic specificity (or maltose-forming amylase) has already been definitively confirmed by both biochemical <cite>Jung2014,Jeon2014</cite> and structural <cite>Park2014</cite> studies. The family GH57 contains further a group of probably non-enzymatic members, i.e. the so-called α-amylase-like proteins having a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
<br />
It is worth mentioning that the two founding members, i.e. the “α-amylases” from ''Dictyoglomus thermophilum'' and ''Pyrococcus furiosus'' are 4-α-glucanotransferases; the former was proven to have transglycosylating activity <cite>Nakajima2004</cite>, whereas the latter was already known to exhibit also the 4-α-glucanotransferase activity <cite>Laderman1993b</cite>.<br />
<br />
A detailed in silico prediction study has indicated a close relatedness of family GH57 to the family GH119 concerning catalytic domain fold, catalytic machinery and conserved sequence regions <cite>Janecek2012</cite>. This original prediction has recently been updated using the AlphFold-generated structural model of a GH119 representative <cite>Polacek2023</cite> and finally confirmed also experimentally by the biochemical characterization of five GH119 members exhibiting a single α-amylase specificity but distinct product profile <cite>Vuillemin2024</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
A direct evidence for the stereochemical outcome of the enzyme-catalyzed reaction has been presented for the branching enzyme from ''Thermus thermophilus'' <cite>Palomo2011</cite> by the NMR analysis of reaction products. The previous observation of a trapped covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> was also a strong evidence that the GH57 enzymes operate with [[retaining|retention]] of anomeric configuration through a [[classical Koshland retaining mechanism]] with retention of anomeric configuration. The X-ray structure of the 4-α-glucanotransferase from ''Thermococcus litoralis'' revealed average distances of 6.72 Å and 6.97 Å between the [[catalytic nucleophile]] (Glu123) and [[general acid/base]] (Asp214) in the free and acarbose-bound forms of the enzyme, respectively, which also supports a retaining mechanism for this family <cite>Imamura2003</cite> (see also <cite>Davies1995</cite>).<br />
<br />
Detailed kinetic studies have been performed on several GH57 enzymes, including the 4-α-glucanotransferases from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> and ''Pyrococcus furiosus'' <cite>Tang2006</cite>, amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>, and branching enzymes from ''Thermococcus kodakaraensis'' <cite>Murakami2006</cite> and ''Thermus thermophilus'' <cite>Palomo2011</cite>.<br />
<br />
== Catalytic Residues ==<br />
The sequences of GH57 members are very diverse. Some sequences are shorter than 400 residues whereas others are longer than 1,500 residues <cite>Janecek2005</cite>. This complicated early efforts to align the GH57 sequences using standard alignment methods. A detailed bioinformatics study by Zona ''et al.'' <cite>Zona2004</cite> focused on all available GH57 sequences at that time and identified five conserved sequence regions. This study used knowledge of the identity of the [[catalytic nucleophile]] (Glu123) in the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001</cite> together with the three-dimensional structure <cite>Imamura2003</cite> (PDB ID [{{PDBlink}}1k1w 1k1w]) that revealed the [[general acid/base]] residue (Asp214).<br />
<br />
The [[catalytic nucleophile]] (a glutamate) and [[general acid/base]] (an aspartate) are located in the conserved sequence regions 3 and 4, respectively. In addition to assignments in ''Thermococcus litoralis'' 4-α-glucanotransferase discussed above, these residues were identified in the amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>. The [[catalytic nucleophile]] was also identified in the α-galactosidase from ''Pyrococcus furiosus'' although no success was achieved in assigning the [[general acid/base]] <cite>vanLieshout2003</cite>. It should be taken into account that some GH57 members, which are only hypothetical enzymes/proteins without any biochemical characterization, may lack one or even both catalytic residues <cite>Zona2004,Janecek2011</cite>.<br />
<br />
Based on the five identified conserved sequence regions, the residues His13, Glu79, Glu216 and Asp354 together with Trp120, Trp221 and Trp357 (''Thermococcus hydrothermalis'' amylopullulanase numbering) were postulated <cite>Zona2004</cite> as important determinants of the individual GH57 enzyme specificities <cite>Janecek2011,Blesak2012,Blesak2013</cite>. Of these, the Trp221 has already been confirmed to contribute to the transglycosylation activity of 4-α-glucanotransferase since the mutant W229H of the enzyme from ''Pyrococcus furiosus'' exhibited markedly decreased transglycosylation activity in comparison with the wild-type counterpart <cite>Tang2006</cite>.<br />
<br />
== Three-dimensional structures ==<br />
The structure of the catalytic domain adopts a (β/α)7-barrel, i.e. the irregular (β/α)8-barrel called a pseudo TIM-barrel. In the case of the ''Thermococcus litoralis'' 4-α-glucanotransferase <cite>Imamura2003</cite> the catalytic domain is succeeded by a C-terminal non-catalytic domain consisting of only β-strands that adopts a twisted β-sandwich fold. In the three-dimensional structure of the α-amylase AmyC from ''Thermotoga maritima'' <cite>Dickmanns2006</cite> (PDB ID [{{PDBlink}}2b5d 2b5d]) (note that the sequence of this enzyme strongly resemles that of a branching enzyme <cite>Blesak2012</cite>), the corresponding catalytic (β/α)7-barrel is followed by a five-helix domain C, a small helical domain B being protruded out of the catalytic pseudo TIM barrel in the place of the loop 2 (i.e. succeeding the strand β2). This structure was found to be closely similar to that of the GH57 member of unknown function from ''Thermus thermophilus'' (PDB ID [{{PDBlink}}1ufa 1ufa]). Two structures of biochemically characterized branching enzymes were solved and published: one from ''Thermus thermophilus'' <cite>Palomo2011</cite> (PDB ID [{{PDBlink}}3p0b 3p0b]) and the other one from ''Thermococcus kodakaraensis'' <cite>Santos2011</cite> (PDB ID [{{PDBlink}}3n8t 3n8t]). The former study <cite>Palomo2011</cite>, importantly, is the first report to prove that a retaining mechanism is employed in the family GH57. Also, the 3-D structure is available for the maltogenic (maltose-forming) amylase from ''Pyrococcus'' sp. ST04 <cite>Park2014</cite> (PDB ID [{{PDBlink}}4cmr 4cmr]). In all cases, the catalytic glutamic acid and aspartic acid residues are located near the C-terminal ends of the strands β4 and β7 of the barrel, respectively <cite>Imamura2003,Dickmanns2006</cite>. There was also a crystallization report in 1995 on a probable GH57 amylopullulanase from ''Pyrococcus woesei'' <cite>Knapp1995</cite>, but the detailed crystallographic analysis of this protein has not been published.<br />
<br />
It is clear that the C-terminal domain cannot be present in some GH57 members with shorter amino acid sequences, e.g., in the α-galactosidases containing less than 400 residues <cite>vanLieshout2003</cite>. On the other hand, some other GH57 members, especially the extra-long amylopullulanases with more than 1,300 residues <cite>Erra-Pujada1999</cite> have to contain even additional domains. One of them could be a longer version of a typical surface layer homology (SLH) motif <cite>Lupas1994</cite> that was named as the so-called SLH motif-bearing domain in the amylopullulanase from ''Thermococcus hydrothermalis'' <cite>Erra-Pujada1999</cite>. This domain was found also in the [[GH15]] glucodextranase from ''Arthrobacter globiformis'' <cite>Mizuno2004</cite>. Remarkably, within the family GH57, the presence of this SLH motif-bearing domain is restricted only for amylopullulanases <cite>Zona2005</cite>.<br />
<br />
It is also worth mentioning that, especially prior the first three-dimensional structure of a GH57 member was available, there were some efforts to join the family GH57 with the main α-amylase family [[GH13]], i.e. the present clan [GH-H] consisting of the families [[GH13]], [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>. Those efforts were focused mainly on looking for some remote homology at the sequence level only <cite>Dong1997,Janecek1998</cite>. Although both GH57 and GH-H employ the same retaining reaction mechanism <cite>Imamura2003,Matsuura1984</cite> the independence of the family GH57 with regard to GH-H clan is at present based not only on differences in the catalytic domain, but more importantly, on the differences in the catalytic machineries and conserved sequence regions <cite>Zona2004,Janecek2002</cite>. As far as other GH families are concerned, the family [[GH38]] α-mannosidase from ''Drosophila melanogaster'' <cite>vandenElsen2001</cite> was revealed to share some structural similarities within the catalytic domain with the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> indicating an eventuality of originating from a common ancestor.<br />
<br />
== Family Firsts ==<br />
;First sterochemistry determination: The first direct evidence of the retaining reaction stereochemistry by product analysis has been delivered by 1H-NMR analysis of the product mixture that confirmed the α-anomeric configuration of the α-1,6-glucosidic bond formed after the incubation of ''Thermus thermophilus'' branching enzyme with amylose <cite>Palomo2011</cite>. Previously, family GH57 enzymes have been indicated to be retaining by trapping of a covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> and a 6.7 Å distance between the catalytic nucleophile and acid/base <cite>Imamura2003</cite>, both of which are consistent with a two-step, double-displacement mechanism. <br />
;First amino acid sequence determination: The first amino acid sequence of the family GH57 was that of the heat stable amylase from an anaerobic thermophilic bacterium ''Dictyoglomus thermophilum'' <cite>Fukusumi1988</cite>. This "α-amylase" was later characterized as 4-α-glucanotransferase <cite>Nakajima2004</cite>. In fact, the family contains many α-amylase-like proteins, i.e. those that exhibit a clear sequence homology with α-amylases, but possess a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
;First conserved sequence regions determination: The five sequence stretches characteristic as conserved regions for the family GH57 were first determined by the bioinformatics study by Zona et al. (2004) <cite>Zona2004</cite>.<br />
;First [[catalytic nucleophile]] identification: The catalytic nucleophile was fist identified by Imamura et al. (2001) <cite>Imamura2001</cite> as Glu123 in the 4-α-glucanotransferase from ''Thermococcus litoralis'' using the 3-ketobutylidene-β-2-chloro-4-nitrophenyl maltopentaoside as a donor.<br />
;First [[general acid/base]] residue identification: Asp214 of the 4-α-glucanotransferase from ''Thermococcus litoralis'' as indicated by the X-ray crystallography and supported by site-directed mutagenesis <cite>Imamura2003</cite> since the D214N mutant exhibited a 10,000-fold decrease of specific activity in comparison with the wild-type enzyme.<br />
;First 3-D structure: The first 3-D structure of a GH57 member was that of the 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2003</cite>.<br />
<br />
== References ==<br />
<biblio><br />
#Henrissat1996 pmid=8687420<br />
#MacGregor2001 pmid=11257505<br />
#Fukusumi1988 pmid=2453362<br />
#Laderman1993a pmid=8226990<br />
#Cantarel2009 pmid=18838391<br />
#Lombard2014 pmid=24270786<br />
#Blesak2012 pmid=22527043<br />
#Li2013 pmid=23001056<br />
#Comfort2008 pmid=18156337<br />
#Blesak2013 pmid=24109595<br />
#Wang2011 pmid=21455739<br />
#Jung2014 pmid=23884203<br />
#Jeon2014 pmid=24835094<br />
#Park2014 pmid=24914977<br />
#Janecek2011 pmid=21786160<br />
#Nakajima2004 pmid=15564678<br />
#Laderman1993b pmid=8226989<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polacek A, Janecek S. "Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57." Biologia 2023; 78(7), 1847-60. [https://doi.org/10.1007/s11756-023-01349-y DOI: 10.1007/s11756-023-01349-y]<br />
#Vuillemin2024 pmid=38280706<br />
<br />
#Palomo2011 pmid=21097495<br />
<br />
#Imamura2003 pmid=12618437<br />
#Imamura2001 pmid=11591160<br />
#Davies1995 pmid=8535779<br />
#Tang2006 pmid=17035108<br />
#Zona2004 pmid=15233783<br />
#Kang2005 pmid=15599521<br />
#Murakami2006 pmid=16885460<br />
#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16) 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])<br />
#vanLieshout2003 van Lieshout JFT, Verhees CH, Ettema TJG, van der Saar S, Imamura H, Matsuzawa H, van der Oost J, de Vos WM. ''Identification and molecular characterization of a novel type of α-galactosidase from Pyrococcus furiosus.'' Biocatal Biotransform 2003; 21(4-5) 243-52. ([http://dx.doi.org/10.1080/10242420310001614342 DOI: 10.1080/10242420310001614342])<br />
#Dickmanns2006 pmid=16510973<br />
#Santos2011 pmid=21104698<br />
#Knapp1995 pmid=8749857<br />
#Erra-Pujada1999 pmid=10322035<br />
#Lupas1994 pmid=8113161<br />
#Mizuno2004 pmid=14660574<br />
#Zona2005 Zona R, Janecek S. ''Relationships between SLH motifs from different glycoside hydrolase families.'' Biologia 2005; 60(Suppl. 16): 115-21. ([http://biologia.savba.sk/Suppl_16/Zona_R.pdf PDF])<br />
#Dong1997 pmid=9293009<br />
#Janecek1998 pmid=9721603<br />
#Matsuura1984 pmid=6609921<br />
#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])<br />
#vandenElsen2001 pmid=11406577<br />
</biblio><br />
<br />
[[Category:Glycoside Hydrolase Families|GH057]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_57&diff=17807Glycoside Hydrolase Family 572024-02-05T11:33:51Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
* [[Responsible Curator]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}}<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH57'''<br />
|-<br />
|'''Clan'''<br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH57.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Substrate specificities ==<br />
[[Glycoside hydrolase]] family 57 was established in 1996 <cite>Henrissat1996</cite> based on the existence of the sequences of two “α-amylases” that were dissimilar to typical family [[GH13]] α-amylases <cite>MacGregor2001</cite>. The two were the heat-stable eubacterial amylase from ''Dictyoglomus thermophilum'' known from 1988 <cite>Fukusumi1988</cite> and the extremely thermostable archaeal amylase from ''Pyrococcus furiosus'' determined in 1993 <cite>Laderman1993a</cite>.<br />
<br />
The family has expanded mainly due to the results of genome sequencing projects. More than a thousand of members are known <cite>Cantarel2009,Lombard2014</cite>, all from prokaryotes (with ~1:4 ratio for Archaea:Bacteria) <cite>Blesak2012</cite>. The enzyme specificities of family GH57 includes α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]), α-galactosidase (EC [{{EClink}}3.2.1.22 3.2.1.22]), amylopullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]), branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]) and 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]).<br />
<br />
An archaeal GH57 amylopullulanase from ''Staphylothermus marinus'' has been described exhibiting also the activity of cyclodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]) <cite>Li2013</cite>. Based on a preliminary observation that the PF0870 protein encoded in the ''Pyrococcus furiosus'' genome produced maltose <cite>Comfort2008</cite>, a group of GH57 members with proposed specificity of maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]) was predicted <cite>Blesak2013</cite> together with another group of non-specified amylases following the partial characterization of an amylolytic enzyme from an uncultured bacterium <cite>Wang2011</cite>. The maltogenic specificity (or maltose-forming amylase) has already been definitively confirmed by both biochemical <cite>Jung2014,Jeon2014</cite> and structural <cite>Park2014</cite> studies. The family GH57 contains further a group of probably non-enzymatic members, i.e. the so-called α-amylase-like proteins having a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
<br />
It is worth mentioning that the two founding members, i.e. the “α-amylases” from ''Dictyoglomus thermophilum'' and ''Pyrococcus furiosus'' are 4-α-glucanotransferases; the former was proven to have transglycosylating activity <cite>Nakajima2004</cite>, whereas the latter was already known to exhibit also the 4-α-glucanotransferase activity <cite>Laderman1993b</cite>.<br />
<br />
A detailed in silico prediction study has indicated a close relatedness of family GH57 to the family GH119 concerning catalytic domain fold, catalytic machinery and conserved sequence regions <cite>Janecek2012</cite>. This original prediction has recently been updated using the AlphFold-generated structural model of a GH119 representative <cite>Polacek2023</cite> and finally confirmed also experimentally by the biochemical characterization of five GH119 members exhibiting a single α-amylase specificity but distinct product profile <cite>Vuillemin2024<cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
A direct evidence for the stereochemical outcome of the enzyme-catalyzed reaction has been presented for the branching enzyme from ''Thermus thermophilus'' <cite>Palomo2011</cite> by the NMR analysis of reaction products. The previous observation of a trapped covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> was also a strong evidence that the GH57 enzymes operate with [[retaining|retention]] of anomeric configuration through a [[classical Koshland retaining mechanism]] with retention of anomeric configuration. The X-ray structure of the 4-α-glucanotransferase from ''Thermococcus litoralis'' revealed average distances of 6.72 Å and 6.97 Å between the [[catalytic nucleophile]] (Glu123) and [[general acid/base]] (Asp214) in the free and acarbose-bound forms of the enzyme, respectively, which also supports a retaining mechanism for this family <cite>Imamura2003</cite> (see also <cite>Davies1995</cite>).<br />
<br />
Detailed kinetic studies have been performed on several GH57 enzymes, including the 4-α-glucanotransferases from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> and ''Pyrococcus furiosus'' <cite>Tang2006</cite>, amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>, and branching enzymes from ''Thermococcus kodakaraensis'' <cite>Murakami2006</cite> and ''Thermus thermophilus'' <cite>Palomo2011</cite>.<br />
<br />
== Catalytic Residues ==<br />
The sequences of GH57 members are very diverse. Some sequences are shorter than 400 residues whereas others are longer than 1,500 residues <cite>Janecek2005</cite>. This complicated early efforts to align the GH57 sequences using standard alignment methods. A detailed bioinformatics study by Zona ''et al.'' <cite>Zona2004</cite> focused on all available GH57 sequences at that time and identified five conserved sequence regions. This study used knowledge of the identity of the [[catalytic nucleophile]] (Glu123) in the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001</cite> together with the three-dimensional structure <cite>Imamura2003</cite> (PDB ID [{{PDBlink}}1k1w 1k1w]) that revealed the [[general acid/base]] residue (Asp214).<br />
<br />
The [[catalytic nucleophile]] (a glutamate) and [[general acid/base]] (an aspartate) are located in the conserved sequence regions 3 and 4, respectively. In addition to assignments in ''Thermococcus litoralis'' 4-α-glucanotransferase discussed above, these residues were identified in the amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>. The [[catalytic nucleophile]] was also identified in the α-galactosidase from ''Pyrococcus furiosus'' although no success was achieved in assigning the [[general acid/base]] <cite>vanLieshout2003</cite>. It should be taken into account that some GH57 members, which are only hypothetical enzymes/proteins without any biochemical characterization, may lack one or even both catalytic residues <cite>Zona2004,Janecek2011</cite>.<br />
<br />
Based on the five identified conserved sequence regions, the residues His13, Glu79, Glu216 and Asp354 together with Trp120, Trp221 and Trp357 (''Thermococcus hydrothermalis'' amylopullulanase numbering) were postulated <cite>Zona2004</cite> as important determinants of the individual GH57 enzyme specificities <cite>Janecek2011,Blesak2012,Blesak2013</cite>. Of these, the Trp221 has already been confirmed to contribute to the transglycosylation activity of 4-α-glucanotransferase since the mutant W229H of the enzyme from ''Pyrococcus furiosus'' exhibited markedly decreased transglycosylation activity in comparison with the wild-type counterpart <cite>Tang2006</cite>.<br />
<br />
== Three-dimensional structures ==<br />
The structure of the catalytic domain adopts a (β/α)7-barrel, i.e. the irregular (β/α)8-barrel called a pseudo TIM-barrel. In the case of the ''Thermococcus litoralis'' 4-α-glucanotransferase <cite>Imamura2003</cite> the catalytic domain is succeeded by a C-terminal non-catalytic domain consisting of only β-strands that adopts a twisted β-sandwich fold. In the three-dimensional structure of the α-amylase AmyC from ''Thermotoga maritima'' <cite>Dickmanns2006</cite> (PDB ID [{{PDBlink}}2b5d 2b5d]) (note that the sequence of this enzyme strongly resemles that of a branching enzyme <cite>Blesak2012</cite>), the corresponding catalytic (β/α)7-barrel is followed by a five-helix domain C, a small helical domain B being protruded out of the catalytic pseudo TIM barrel in the place of the loop 2 (i.e. succeeding the strand β2). This structure was found to be closely similar to that of the GH57 member of unknown function from ''Thermus thermophilus'' (PDB ID [{{PDBlink}}1ufa 1ufa]). Two structures of biochemically characterized branching enzymes were solved and published: one from ''Thermus thermophilus'' <cite>Palomo2011</cite> (PDB ID [{{PDBlink}}3p0b 3p0b]) and the other one from ''Thermococcus kodakaraensis'' <cite>Santos2011</cite> (PDB ID [{{PDBlink}}3n8t 3n8t]). The former study <cite>Palomo2011</cite>, importantly, is the first report to prove that a retaining mechanism is employed in the family GH57. Also, the 3-D structure is available for the maltogenic (maltose-forming) amylase from ''Pyrococcus'' sp. ST04 <cite>Park2014</cite> (PDB ID [{{PDBlink}}4cmr 4cmr]). In all cases, the catalytic glutamic acid and aspartic acid residues are located near the C-terminal ends of the strands β4 and β7 of the barrel, respectively <cite>Imamura2003,Dickmanns2006</cite>. There was also a crystallization report in 1995 on a probable GH57 amylopullulanase from ''Pyrococcus woesei'' <cite>Knapp1995</cite>, but the detailed crystallographic analysis of this protein has not been published.<br />
<br />
It is clear that the C-terminal domain cannot be present in some GH57 members with shorter amino acid sequences, e.g., in the α-galactosidases containing less than 400 residues <cite>vanLieshout2003</cite>. On the other hand, some other GH57 members, especially the extra-long amylopullulanases with more than 1,300 residues <cite>Erra-Pujada1999</cite> have to contain even additional domains. One of them could be a longer version of a typical surface layer homology (SLH) motif <cite>Lupas1994</cite> that was named as the so-called SLH motif-bearing domain in the amylopullulanase from ''Thermococcus hydrothermalis'' <cite>Erra-Pujada1999</cite>. This domain was found also in the [[GH15]] glucodextranase from ''Arthrobacter globiformis'' <cite>Mizuno2004</cite>. Remarkably, within the family GH57, the presence of this SLH motif-bearing domain is restricted only for amylopullulanases <cite>Zona2005</cite>.<br />
<br />
It is also worth mentioning that, especially prior the first three-dimensional structure of a GH57 member was available, there were some efforts to join the family GH57 with the main α-amylase family [[GH13]], i.e. the present clan [GH-H] consisting of the families [[GH13]], [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>. Those efforts were focused mainly on looking for some remote homology at the sequence level only <cite>Dong1997,Janecek1998</cite>. Although both GH57 and GH-H employ the same retaining reaction mechanism <cite>Imamura2003,Matsuura1984</cite> the independence of the family GH57 with regard to GH-H clan is at present based not only on differences in the catalytic domain, but more importantly, on the differences in the catalytic machineries and conserved sequence regions <cite>Zona2004,Janecek2002</cite>. As far as other GH families are concerned, the family [[GH38]] α-mannosidase from ''Drosophila melanogaster'' <cite>vandenElsen2001</cite> was revealed to share some structural similarities within the catalytic domain with the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> indicating an eventuality of originating from a common ancestor.<br />
<br />
== Family Firsts ==<br />
;First sterochemistry determination: The first direct evidence of the retaining reaction stereochemistry by product analysis has been delivered by 1H-NMR analysis of the product mixture that confirmed the α-anomeric configuration of the α-1,6-glucosidic bond formed after the incubation of ''Thermus thermophilus'' branching enzyme with amylose <cite>Palomo2011</cite>. Previously, family GH57 enzymes have been indicated to be retaining by trapping of a covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> and a 6.7 Å distance between the catalytic nucleophile and acid/base <cite>Imamura2003</cite>, both of which are consistent with a two-step, double-displacement mechanism. <br />
;First amino acid sequence determination: The first amino acid sequence of the family GH57 was that of the heat stable amylase from an anaerobic thermophilic bacterium ''Dictyoglomus thermophilum'' <cite>Fukusumi1988</cite>. This "α-amylase" was later characterized as 4-α-glucanotransferase <cite>Nakajima2004</cite>. In fact, the family contains many α-amylase-like proteins, i.e. those that exhibit a clear sequence homology with α-amylases, but possess a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
;First conserved sequence regions determination: The five sequence stretches characteristic as conserved regions for the family GH57 were first determined by the bioinformatics study by Zona et al. (2004) <cite>Zona2004</cite>.<br />
;First [[catalytic nucleophile]] identification: The catalytic nucleophile was fist identified by Imamura et al. (2001) <cite>Imamura2001</cite> as Glu123 in the 4-α-glucanotransferase from ''Thermococcus litoralis'' using the 3-ketobutylidene-β-2-chloro-4-nitrophenyl maltopentaoside as a donor.<br />
;First [[general acid/base]] residue identification: Asp214 of the 4-α-glucanotransferase from ''Thermococcus litoralis'' as indicated by the X-ray crystallography and supported by site-directed mutagenesis <cite>Imamura2003</cite> since the D214N mutant exhibited a 10,000-fold decrease of specific activity in comparison with the wild-type enzyme.<br />
;First 3-D structure: The first 3-D structure of a GH57 member was that of the 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2003</cite>.<br />
<br />
== References ==<br />
<biblio><br />
#Henrissat1996 pmid=8687420<br />
#MacGregor2001 pmid=11257505<br />
#Fukusumi1988 pmid=2453362<br />
#Laderman1993a pmid=8226990<br />
#Cantarel2009 pmid=18838391<br />
#Lombard2014 pmid=24270786<br />
#Blesak2012 pmid=22527043<br />
#Li2013 pmid=23001056<br />
#Comfort2008 pmid=18156337<br />
#Blesak2013 pmid=24109595<br />
#Wang2011 pmid=21455739<br />
#Jung2014 pmid=23884203<br />
#Jeon2014 pmid=24835094<br />
#Park2014 pmid=24914977<br />
#Janecek2011 pmid=21786160<br />
#Nakajima2004 pmid=15564678<br />
#Laderman1993b pmid=8226989<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polacek A, Janecek S. "Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57." Biologia 2023; 78(7), 1847-60. [https://doi.org/10.1007/s11756-023-01349-y DOI: 10.1007/s11756-023-01349-y]<br />
#Vuillemin2024 pmid=38280706<br />
<br />
#Palomo2011 pmid=21097495<br />
<br />
#Imamura2003 pmid=12618437<br />
#Imamura2001 pmid=11591160<br />
#Davies1995 pmid=8535779<br />
#Tang2006 pmid=17035108<br />
#Zona2004 pmid=15233783<br />
#Kang2005 pmid=15599521<br />
#Murakami2006 pmid=16885460<br />
#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16) 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])<br />
#vanLieshout2003 van Lieshout JFT, Verhees CH, Ettema TJG, van der Saar S, Imamura H, Matsuzawa H, van der Oost J, de Vos WM. ''Identification and molecular characterization of a novel type of α-galactosidase from Pyrococcus furiosus.'' Biocatal Biotransform 2003; 21(4-5) 243-52. ([http://dx.doi.org/10.1080/10242420310001614342 DOI: 10.1080/10242420310001614342])<br />
#Dickmanns2006 pmid=16510973<br />
#Santos2011 pmid=21104698<br />
#Knapp1995 pmid=8749857<br />
#Erra-Pujada1999 pmid=10322035<br />
#Lupas1994 pmid=8113161<br />
#Mizuno2004 pmid=14660574<br />
#Zona2005 Zona R, Janecek S. ''Relationships between SLH motifs from different glycoside hydrolase families.'' Biologia 2005; 60(Suppl. 16): 115-21. ([http://biologia.savba.sk/Suppl_16/Zona_R.pdf PDF])<br />
#Dong1997 pmid=9293009<br />
#Janecek1998 pmid=9721603<br />
#Matsuura1984 pmid=6609921<br />
#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])<br />
#vandenElsen2001 pmid=11406577<br />
</biblio><br />
<br />
[[Category:Glycoside Hydrolase Families|GH057]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_57&diff=17806Glycoside Hydrolase Family 572024-02-05T11:29:26Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
* [[Responsible Curator]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}}<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH57'''<br />
|-<br />
|'''Clan'''<br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH57.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Substrate specificities ==<br />
[[Glycoside hydrolase]] family 57 was established in 1996 <cite>Henrissat1996</cite> based on the existence of the sequences of two “α-amylases” that were dissimilar to typical family [[GH13]] α-amylases <cite>MacGregor2001</cite>. The two were the heat-stable eubacterial amylase from ''Dictyoglomus thermophilum'' known from 1988 <cite>Fukusumi1988</cite> and the extremely thermostable archaeal amylase from ''Pyrococcus furiosus'' determined in 1993 <cite>Laderman1993a</cite>.<br />
<br />
The family has expanded mainly due to the results of genome sequencing projects. More than a thousand of members are known <cite>Cantarel2009,Lombard2014</cite>, all from prokaryotes (with ~1:4 ratio for Archaea:Bacteria) <cite>Blesak2012</cite>. The enzyme specificities of family GH57 includes α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]), α-galactosidase (EC [{{EClink}}3.2.1.22 3.2.1.22]), amylopullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]), branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]) and 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]).<br />
<br />
An archaeal GH57 amylopullulanase from ''Staphylothermus marinus'' has been described exhibiting also the activity of cyclodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]) <cite>Li2013</cite>. Based on a preliminary observation that the PF0870 protein encoded in the ''Pyrococcus furiosus'' genome produced maltose <cite>Comfort2008</cite>, a group of GH57 members with proposed specificity of maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]) was predicted <cite>Blesak2013</cite> together with another group of non-specified amylases following the partial characterization of an amylolytic enzyme from an uncultured bacterium <cite>Wang2011</cite>. The maltogenic specificity (or maltose-forming amylase) has already been definitively confirmed by both biochemical <cite>Jung2014,Jeon2014</cite> and structural <cite>Park2014</cite> studies. The family GH57 contains further a group of probably non-enzymatic members, i.e. the so-called α-amylase-like proteins having a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
<br />
It is worth mentioning that the two founding members, i.e. the “α-amylases” from ''Dictyoglomus thermophilum'' and ''Pyrococcus furiosus'' are 4-α-glucanotransferases; the former was proven to have transglycosylating activity <cite>Nakajima2004</cite>, whereas the latter was already known to exhibit also the 4-α-glucanotransferase activity <cite>Laderman1993b</cite>.<br />
<br />
A detailed in silico prediction study has indicated a close relatedness of family GH57 to the family GH119 concerning catalytic domain fold, catalytic machinery and conserved sequence regions <cite>Janecek2012</cite>. This original prediction has recently been updated <cite>Polacek2023</cite> and finally confirmed by experimental characterization of the <br />
<br />
== Kinetics and Mechanism ==<br />
A direct evidence for the stereochemical outcome of the enzyme-catalyzed reaction has been presented for the branching enzyme from ''Thermus thermophilus'' <cite>Palomo2011</cite> by the NMR analysis of reaction products. The previous observation of a trapped covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> was also a strong evidence that the GH57 enzymes operate with [[retaining|retention]] of anomeric configuration through a [[classical Koshland retaining mechanism]] with retention of anomeric configuration. The X-ray structure of the 4-α-glucanotransferase from ''Thermococcus litoralis'' revealed average distances of 6.72 Å and 6.97 Å between the [[catalytic nucleophile]] (Glu123) and [[general acid/base]] (Asp214) in the free and acarbose-bound forms of the enzyme, respectively, which also supports a retaining mechanism for this family <cite>Imamura2003</cite> (see also <cite>Davies1995</cite>).<br />
<br />
Detailed kinetic studies have been performed on several GH57 enzymes, including the 4-α-glucanotransferases from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> and ''Pyrococcus furiosus'' <cite>Tang2006</cite>, amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>, and branching enzymes from ''Thermococcus kodakaraensis'' <cite>Murakami2006</cite> and ''Thermus thermophilus'' <cite>Palomo2011</cite>.<br />
<br />
== Catalytic Residues ==<br />
The sequences of GH57 members are very diverse. Some sequences are shorter than 400 residues whereas others are longer than 1,500 residues <cite>Janecek2005</cite>. This complicated early efforts to align the GH57 sequences using standard alignment methods. A detailed bioinformatics study by Zona ''et al.'' <cite>Zona2004</cite> focused on all available GH57 sequences at that time and identified five conserved sequence regions. This study used knowledge of the identity of the [[catalytic nucleophile]] (Glu123) in the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001</cite> together with the three-dimensional structure <cite>Imamura2003</cite> (PDB ID [{{PDBlink}}1k1w 1k1w]) that revealed the [[general acid/base]] residue (Asp214).<br />
<br />
The [[catalytic nucleophile]] (a glutamate) and [[general acid/base]] (an aspartate) are located in the conserved sequence regions 3 and 4, respectively. In addition to assignments in ''Thermococcus litoralis'' 4-α-glucanotransferase discussed above, these residues were identified in the amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>. The [[catalytic nucleophile]] was also identified in the α-galactosidase from ''Pyrococcus furiosus'' although no success was achieved in assigning the [[general acid/base]] <cite>vanLieshout2003</cite>. It should be taken into account that some GH57 members, which are only hypothetical enzymes/proteins without any biochemical characterization, may lack one or even both catalytic residues <cite>Zona2004,Janecek2011</cite>.<br />
<br />
Based on the five identified conserved sequence regions, the residues His13, Glu79, Glu216 and Asp354 together with Trp120, Trp221 and Trp357 (''Thermococcus hydrothermalis'' amylopullulanase numbering) were postulated <cite>Zona2004</cite> as important determinants of the individual GH57 enzyme specificities <cite>Janecek2011,Blesak2012,Blesak2013</cite>. Of these, the Trp221 has already been confirmed to contribute to the transglycosylation activity of 4-α-glucanotransferase since the mutant W229H of the enzyme from ''Pyrococcus furiosus'' exhibited markedly decreased transglycosylation activity in comparison with the wild-type counterpart <cite>Tang2006</cite>.<br />
<br />
== Three-dimensional structures ==<br />
The structure of the catalytic domain adopts a (β/α)7-barrel, i.e. the irregular (β/α)8-barrel called a pseudo TIM-barrel. In the case of the ''Thermococcus litoralis'' 4-α-glucanotransferase <cite>Imamura2003</cite> the catalytic domain is succeeded by a C-terminal non-catalytic domain consisting of only β-strands that adopts a twisted β-sandwich fold. In the three-dimensional structure of the α-amylase AmyC from ''Thermotoga maritima'' <cite>Dickmanns2006</cite> (PDB ID [{{PDBlink}}2b5d 2b5d]) (note that the sequence of this enzyme strongly resemles that of a branching enzyme <cite>Blesak2012</cite>), the corresponding catalytic (β/α)7-barrel is followed by a five-helix domain C, a small helical domain B being protruded out of the catalytic pseudo TIM barrel in the place of the loop 2 (i.e. succeeding the strand β2). This structure was found to be closely similar to that of the GH57 member of unknown function from ''Thermus thermophilus'' (PDB ID [{{PDBlink}}1ufa 1ufa]). Two structures of biochemically characterized branching enzymes were solved and published: one from ''Thermus thermophilus'' <cite>Palomo2011</cite> (PDB ID [{{PDBlink}}3p0b 3p0b]) and the other one from ''Thermococcus kodakaraensis'' <cite>Santos2011</cite> (PDB ID [{{PDBlink}}3n8t 3n8t]). The former study <cite>Palomo2011</cite>, importantly, is the first report to prove that a retaining mechanism is employed in the family GH57. Also, the 3-D structure is available for the maltogenic (maltose-forming) amylase from ''Pyrococcus'' sp. ST04 <cite>Park2014</cite> (PDB ID [{{PDBlink}}4cmr 4cmr]). In all cases, the catalytic glutamic acid and aspartic acid residues are located near the C-terminal ends of the strands β4 and β7 of the barrel, respectively <cite>Imamura2003,Dickmanns2006</cite>. There was also a crystallization report in 1995 on a probable GH57 amylopullulanase from ''Pyrococcus woesei'' <cite>Knapp1995</cite>, but the detailed crystallographic analysis of this protein has not been published.<br />
<br />
It is clear that the C-terminal domain cannot be present in some GH57 members with shorter amino acid sequences, e.g., in the α-galactosidases containing less than 400 residues <cite>vanLieshout2003</cite>. On the other hand, some other GH57 members, especially the extra-long amylopullulanases with more than 1,300 residues <cite>Erra-Pujada1999</cite> have to contain even additional domains. One of them could be a longer version of a typical surface layer homology (SLH) motif <cite>Lupas1994</cite> that was named as the so-called SLH motif-bearing domain in the amylopullulanase from ''Thermococcus hydrothermalis'' <cite>Erra-Pujada1999</cite>. This domain was found also in the [[GH15]] glucodextranase from ''Arthrobacter globiformis'' <cite>Mizuno2004</cite>. Remarkably, within the family GH57, the presence of this SLH motif-bearing domain is restricted only for amylopullulanases <cite>Zona2005</cite>.<br />
<br />
It is also worth mentioning that, especially prior the first three-dimensional structure of a GH57 member was available, there were some efforts to join the family GH57 with the main α-amylase family [[GH13]], i.e. the present clan [GH-H] consisting of the families [[GH13]], [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>. Those efforts were focused mainly on looking for some remote homology at the sequence level only <cite>Dong1997,Janecek1998</cite>. Although both GH57 and GH-H employ the same retaining reaction mechanism <cite>Imamura2003,Matsuura1984</cite> the independence of the family GH57 with regard to GH-H clan is at present based not only on differences in the catalytic domain, but more importantly, on the differences in the catalytic machineries and conserved sequence regions <cite>Zona2004,Janecek2002</cite>. As far as other GH families are concerned, the family [[GH38]] α-mannosidase from ''Drosophila melanogaster'' <cite>vandenElsen2001</cite> was revealed to share some structural similarities within the catalytic domain with the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> indicating an eventuality of originating from a common ancestor.<br />
<br />
== Family Firsts ==<br />
;First sterochemistry determination: The first direct evidence of the retaining reaction stereochemistry by product analysis has been delivered by 1H-NMR analysis of the product mixture that confirmed the α-anomeric configuration of the α-1,6-glucosidic bond formed after the incubation of ''Thermus thermophilus'' branching enzyme with amylose <cite>Palomo2011</cite>. Previously, family GH57 enzymes have been indicated to be retaining by trapping of a covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> and a 6.7 Å distance between the catalytic nucleophile and acid/base <cite>Imamura2003</cite>, both of which are consistent with a two-step, double-displacement mechanism. <br />
;First amino acid sequence determination: The first amino acid sequence of the family GH57 was that of the heat stable amylase from an anaerobic thermophilic bacterium ''Dictyoglomus thermophilum'' <cite>Fukusumi1988</cite>. This "α-amylase" was later characterized as 4-α-glucanotransferase <cite>Nakajima2004</cite>. In fact, the family contains many α-amylase-like proteins, i.e. those that exhibit a clear sequence homology with α-amylases, but possess a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
;First conserved sequence regions determination: The five sequence stretches characteristic as conserved regions for the family GH57 were first determined by the bioinformatics study by Zona et al. (2004) <cite>Zona2004</cite>.<br />
;First [[catalytic nucleophile]] identification: The catalytic nucleophile was fist identified by Imamura et al. (2001) <cite>Imamura2001</cite> as Glu123 in the 4-α-glucanotransferase from ''Thermococcus litoralis'' using the 3-ketobutylidene-β-2-chloro-4-nitrophenyl maltopentaoside as a donor.<br />
;First [[general acid/base]] residue identification: Asp214 of the 4-α-glucanotransferase from ''Thermococcus litoralis'' as indicated by the X-ray crystallography and supported by site-directed mutagenesis <cite>Imamura2003</cite> since the D214N mutant exhibited a 10,000-fold decrease of specific activity in comparison with the wild-type enzyme.<br />
;First 3-D structure: The first 3-D structure of a GH57 member was that of the 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2003</cite>.<br />
<br />
== References ==<br />
<biblio><br />
#Henrissat1996 pmid=8687420<br />
#MacGregor2001 pmid=11257505<br />
#Fukusumi1988 pmid=2453362<br />
#Laderman1993a pmid=8226990<br />
#Cantarel2009 pmid=18838391<br />
#Lombard2014 pmid=24270786<br />
#Blesak2012 pmid=22527043<br />
#Li2013 pmid=23001056<br />
#Comfort2008 pmid=18156337<br />
#Blesak2013 pmid=24109595<br />
#Wang2011 pmid=21455739<br />
#Jung2014 pmid=23884203<br />
#Jeon2014 pmid=24835094<br />
#Park2014 pmid=24914977<br />
#Janecek2011 pmid=21786160<br />
#Nakajima2004 pmid=15564678<br />
#Laderman1993b pmid=8226989<br />
#Janecek2012 pmid=22819817<br />
#Polacek2023 Polacek A, Janecek S. "Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57." Biologia 2023; 78(7), 1847-60. [https://doi.org/10.1007/s11756-023-01349-y DOI: 10.1007/s11756-023-01349-y]<br />
#Palomo2011 pmid=21097495<br />
#Imamura2003 pmid=12618437<br />
#Imamura2001 pmid=11591160<br />
#Davies1995 pmid=8535779<br />
#Tang2006 pmid=17035108<br />
#Zona2004 pmid=15233783<br />
#Kang2005 pmid=15599521<br />
#Murakami2006 pmid=16885460<br />
#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16) 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])<br />
#vanLieshout2003 van Lieshout JFT, Verhees CH, Ettema TJG, van der Saar S, Imamura H, Matsuzawa H, van der Oost J, de Vos WM. ''Identification and molecular characterization of a novel type of α-galactosidase from Pyrococcus furiosus.'' Biocatal Biotransform 2003; 21(4-5) 243-52. ([http://dx.doi.org/10.1080/10242420310001614342 DOI: 10.1080/10242420310001614342])<br />
#Dickmanns2006 pmid=16510973<br />
#Santos2011 pmid=21104698<br />
#Knapp1995 pmid=8749857<br />
#Erra-Pujada1999 pmid=10322035<br />
#Lupas1994 pmid=8113161<br />
#Mizuno2004 pmid=14660574<br />
#Zona2005 Zona R, Janecek S. ''Relationships between SLH motifs from different glycoside hydrolase families.'' Biologia 2005; 60(Suppl. 16): 115-21. ([http://biologia.savba.sk/Suppl_16/Zona_R.pdf PDF])<br />
#Dong1997 pmid=9293009<br />
#Janecek1998 pmid=9721603<br />
#Matsuura1984 pmid=6609921<br />
#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])<br />
#vandenElsen2001 pmid=11406577<br />
</biblio><br />
<br />
[[Category:Glycoside Hydrolase Families|GH057]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_57&diff=17805Glycoside Hydrolase Family 572024-02-05T11:28:15Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
* [[Responsible Curator]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}}<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH57'''<br />
|-<br />
|'''Clan'''<br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH57.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Substrate specificities ==<br />
[[Glycoside hydrolase]] family 57 was established in 1996 <cite>Henrissat1996</cite> based on the existence of the sequences of two “α-amylases” that were dissimilar to typical family [[GH13]] α-amylases <cite>MacGregor2001</cite>. The two were the heat-stable eubacterial amylase from ''Dictyoglomus thermophilum'' known from 1988 <cite>Fukusumi1988</cite> and the extremely thermostable archaeal amylase from ''Pyrococcus furiosus'' determined in 1993 <cite>Laderman1993a</cite>.<br />
<br />
The family has expanded mainly due to the results of genome sequencing projects. More than a thousand of members are known <cite>Cantarel2009,Lombard2014</cite>, all from prokaryotes (with ~1:4 ratio for Archaea:Bacteria) <cite>Blesak2012</cite>. The enzyme specificities of family GH57 includes α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]), α-galactosidase (EC [{{EClink}}3.2.1.22 3.2.1.22]), amylopullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]), branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]) and 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]).<br />
<br />
An archaeal GH57 amylopullulanase from ''Staphylothermus marinus'' has been described exhibiting also the activity of cyclodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]) <cite>Li2013</cite>. Based on a preliminary observation that the PF0870 protein encoded in the ''Pyrococcus furiosus'' genome produced maltose <cite>Comfort2008</cite>, a group of GH57 members with proposed specificity of maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]) was predicted <cite>Blesak2013</cite> together with another group of non-specified amylases following the partial characterization of an amylolytic enzyme from an uncultured bacterium <cite>Wang2011</cite>. The maltogenic specificity (or maltose-forming amylase) has already been definitively confirmed by both biochemical <cite>Jung2014,Jeon2014</cite> and structural <cite>Park2014</cite> studies. The family GH57 contains further a group of probably non-enzymatic members, i.e. the so-called α-amylase-like proteins having a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
<br />
It is worth mentioning that the two founding members, i.e. the “α-amylases” from ''Dictyoglomus thermophilum'' and ''Pyrococcus furiosus'' are 4-α-glucanotransferases; the former was proven to have transglycosylating activity <cite>Nakajima2004</cite>, whereas the latter was already known to exhibit also the 4-α-glucanotransferase activity <cite>Laderman1993b</cite>.<br />
<br />
A detailed in silico prediction study has indicated a close relatedness of family GH57 to the family GH119 concerning catalytic domain fold, catalytic machinery and conserved sequence regions <cite>Janecek2012</cite>. This original prediction has recently been updated <cite>Polacek2023</cite> and finally confirmed by experimental characterization of the <br />
<br />
== Kinetics and Mechanism ==<br />
A direct evidence for the stereochemical outcome of the enzyme-catalyzed reaction has been presented for the branching enzyme from ''Thermus thermophilus'' <cite>Palomo2011</cite> by the NMR analysis of reaction products. The previous observation of a trapped covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> was also a strong evidence that the GH57 enzymes operate with [[retaining|retention]] of anomeric configuration through a [[classical Koshland retaining mechanism]] with retention of anomeric configuration. The X-ray structure of the 4-α-glucanotransferase from ''Thermococcus litoralis'' revealed average distances of 6.72 Å and 6.97 Å between the [[catalytic nucleophile]] (Glu123) and [[general acid/base]] (Asp214) in the free and acarbose-bound forms of the enzyme, respectively, which also supports a retaining mechanism for this family <cite>Imamura2003</cite> (see also <cite>Davies1995</cite>).<br />
<br />
Detailed kinetic studies have been performed on several GH57 enzymes, including the 4-α-glucanotransferases from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> and ''Pyrococcus furiosus'' <cite>Tang2006</cite>, amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>, and branching enzymes from ''Thermococcus kodakaraensis'' <cite>Murakami2006</cite> and ''Thermus thermophilus'' <cite>Palomo2011</cite>.<br />
<br />
== Catalytic Residues ==<br />
The sequences of GH57 members are very diverse. Some sequences are shorter than 400 residues whereas others are longer than 1,500 residues <cite>Janecek2005</cite>. This complicated early efforts to align the GH57 sequences using standard alignment methods. A detailed bioinformatics study by Zona ''et al.'' <cite>Zona2004</cite> focused on all available GH57 sequences at that time and identified five conserved sequence regions. This study used knowledge of the identity of the [[catalytic nucleophile]] (Glu123) in the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001</cite> together with the three-dimensional structure <cite>Imamura2003</cite> (PDB ID [{{PDBlink}}1k1w 1k1w]) that revealed the [[general acid/base]] residue (Asp214).<br />
<br />
The [[catalytic nucleophile]] (a glutamate) and [[general acid/base]] (an aspartate) are located in the conserved sequence regions 3 and 4, respectively. In addition to assignments in ''Thermococcus litoralis'' 4-α-glucanotransferase discussed above, these residues were identified in the amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>. The [[catalytic nucleophile]] was also identified in the α-galactosidase from ''Pyrococcus furiosus'' although no success was achieved in assigning the [[general acid/base]] <cite>vanLieshout2003</cite>. It should be taken into account that some GH57 members, which are only hypothetical enzymes/proteins without any biochemical characterization, may lack one or even both catalytic residues <cite>Zona2004,Janecek2011</cite>.<br />
<br />
Based on the five identified conserved sequence regions, the residues His13, Glu79, Glu216 and Asp354 together with Trp120, Trp221 and Trp357 (''Thermococcus hydrothermalis'' amylopullulanase numbering) were postulated <cite>Zona2004</cite> as important determinants of the individual GH57 enzyme specificities <cite>Janecek2011,Blesak2012,Blesak2013</cite>. Of these, the Trp221 has already been confirmed to contribute to the transglycosylation activity of 4-α-glucanotransferase since the mutant W229H of the enzyme from ''Pyrococcus furiosus'' exhibited markedly decreased transglycosylation activity in comparison with the wild-type counterpart <cite>Tang2006</cite>.<br />
<br />
== Three-dimensional structures ==<br />
The structure of the catalytic domain adopts a (β/α)7-barrel, i.e. the irregular (β/α)8-barrel called a pseudo TIM-barrel. In the case of the ''Thermococcus litoralis'' 4-α-glucanotransferase <cite>Imamura2003</cite> the catalytic domain is succeeded by a C-terminal non-catalytic domain consisting of only β-strands that adopts a twisted β-sandwich fold. In the three-dimensional structure of the α-amylase AmyC from ''Thermotoga maritima'' <cite>Dickmanns2006</cite> (PDB ID [{{PDBlink}}2b5d 2b5d]) (note that the sequence of this enzyme strongly resemles that of a branching enzyme <cite>Blesak2012</cite>), the corresponding catalytic (β/α)7-barrel is followed by a five-helix domain C, a small helical domain B being protruded out of the catalytic pseudo TIM barrel in the place of the loop 2 (i.e. succeeding the strand β2). This structure was found to be closely similar to that of the GH57 member of unknown function from ''Thermus thermophilus'' (PDB ID [{{PDBlink}}1ufa 1ufa]). Two structures of biochemically characterized branching enzymes were solved and published: one from ''Thermus thermophilus'' <cite>Palomo2011</cite> (PDB ID [{{PDBlink}}3p0b 3p0b]) and the other one from ''Thermococcus kodakaraensis'' <cite>Santos2011</cite> (PDB ID [{{PDBlink}}3n8t 3n8t]). The former study <cite>Palomo2011</cite>, importantly, is the first report to prove that a retaining mechanism is employed in the family GH57. Also, the 3-D structure is available for the maltogenic (maltose-forming) amylase from ''Pyrococcus'' sp. ST04 <cite>Park2014</cite> (PDB ID [{{PDBlink}}4cmr 4cmr]). In all cases, the catalytic glutamic acid and aspartic acid residues are located near the C-terminal ends of the strands β4 and β7 of the barrel, respectively <cite>Imamura2003,Dickmanns2006</cite>. There was also a crystallization report in 1995 on a probable GH57 amylopullulanase from ''Pyrococcus woesei'' <cite>Knapp1995</cite>, but the detailed crystallographic analysis of this protein has not been published.<br />
<br />
It is clear that the C-terminal domain cannot be present in some GH57 members with shorter amino acid sequences, e.g., in the α-galactosidases containing less than 400 residues <cite>vanLieshout2003</cite>. On the other hand, some other GH57 members, especially the extra-long amylopullulanases with more than 1,300 residues <cite>Erra-Pujada1999</cite> have to contain even additional domains. One of them could be a longer version of a typical surface layer homology (SLH) motif <cite>Lupas1994</cite> that was named as the so-called SLH motif-bearing domain in the amylopullulanase from ''Thermococcus hydrothermalis'' <cite>Erra-Pujada1999</cite>. This domain was found also in the [[GH15]] glucodextranase from ''Arthrobacter globiformis'' <cite>Mizuno2004</cite>. Remarkably, within the family GH57, the presence of this SLH motif-bearing domain is restricted only for amylopullulanases <cite>Zona2005</cite>.<br />
<br />
It is also worth mentioning that, especially prior the first three-dimensional structure of a GH57 member was available, there were some efforts to join the family GH57 with the main α-amylase family [[GH13]], i.e. the present clan [GH-H] consisting of the families [[GH13]], [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>. Those efforts were focused mainly on looking for some remote homology at the sequence level only <cite>Dong1997,Janecek1998</cite>. Although both GH57 and GH-H employ the same retaining reaction mechanism <cite>Imamura2003,Matsuura1984</cite> the independence of the family GH57 with regard to GH-H clan is at present based not only on differences in the catalytic domain, but more importantly, on the differences in the catalytic machineries and conserved sequence regions <cite>Zona2004,Janecek2002</cite>. As far as other GH families are concerned, the family [[GH38]] α-mannosidase from ''Drosophila melanogaster'' <cite>vandenElsen2001</cite> was revealed to share some structural similarities within the catalytic domain with the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> indicating an eventuality of originating from a common ancestor.<br />
<br />
== Family Firsts ==<br />
;First sterochemistry determination: The first direct evidence of the retaining reaction stereochemistry by product analysis has been delivered by 1H-NMR analysis of the product mixture that confirmed the α-anomeric configuration of the α-1,6-glucosidic bond formed after the incubation of ''Thermus thermophilus'' branching enzyme with amylose <cite>Palomo2011</cite>. Previously, family GH57 enzymes have been indicated to be retaining by trapping of a covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> and a 6.7 Å distance between the catalytic nucleophile and acid/base <cite>Imamura2003</cite>, both of which are consistent with a two-step, double-displacement mechanism. <br />
;First amino acid sequence determination: The first amino acid sequence of the family GH57 was that of the heat stable amylase from an anaerobic thermophilic bacterium ''Dictyoglomus thermophilum'' <cite>Fukusumi1988</cite>. This "α-amylase" was later characterized as 4-α-glucanotransferase <cite>Nakajima2004</cite>. In fact, the family contains many α-amylase-like proteins, i.e. those that exhibit a clear sequence homology with α-amylases, but possess a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
;First conserved sequence regions determination: The five sequence stretches characteristic as conserved regions for the family GH57 were first determined by the bioinformatics study by Zona et al. (2004) <cite>Zona2004</cite>.<br />
;First [[catalytic nucleophile]] identification: The catalytic nucleophile was fist identified by Imamura et al. (2001) <cite>Imamura2001</cite> as Glu123 in the 4-α-glucanotransferase from ''Thermococcus litoralis'' using the 3-ketobutylidene-β-2-chloro-4-nitrophenyl maltopentaoside as a donor.<br />
;First [[general acid/base]] residue identification: Asp214 of the 4-α-glucanotransferase from ''Thermococcus litoralis'' as indicated by the X-ray crystallography and supported by site-directed mutagenesis <cite>Imamura2003</cite> since the D214N mutant exhibited a 10,000-fold decrease of specific activity in comparison with the wild-type enzyme.<br />
;First 3-D structure: The first 3-D structure of a GH57 member was that of the 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2003</cite>.<br />
<br />
== References ==<br />
<biblio><br />
#Henrissat1996 pmid=8687420<br />
#MacGregor2001 pmid=11257505<br />
#Fukusumi1988 pmid=2453362<br />
#Laderman1993a pmid=8226990<br />
#Cantarel2009 pmid=18838391<br />
#Lombard2014 pmid=24270786<br />
#Blesak2012 pmid=22527043<br />
#Li2013 pmid=23001056<br />
#Comfort2008 pmid=18156337<br />
#Blesak2013 pmid=24109595<br />
#Wang2011 pmid=21455739<br />
#Jung2014 pmid=23884203<br />
#Jeon2014 pmid=24835094<br />
#Park2014 pmid=24914977<br />
#Janecek2011 pmid=21786160<br />
#Nakajima2004 pmid=15564678<br />
#Laderman1993b pmid=8226989<br />
#Janecek2012 pmid=22819817<br />
<br />
#Polacek2023 Polacek A, Janecek S. "Sequence-structural features and evolution of the α-amylase family GH119 revealed by the in silico analysis of its relatedness to the family GH57." Biologia 2023; 78(7), 1847-60. ([https://doi.org/10.1007/s11756-023-01349-y DOI: 10.1007/s11756-023-01349-y])<br />
<br />
#Palomo2011 pmid=21097495<br />
<br />
#Imamura2003 pmid=12618437<br />
#Imamura2001 pmid=11591160<br />
#Davies1995 pmid=8535779<br />
#Tang2006 pmid=17035108<br />
#Zona2004 pmid=15233783<br />
#Kang2005 pmid=15599521<br />
#Murakami2006 pmid=16885460<br />
#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16) 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])<br />
#vanLieshout2003 van Lieshout JFT, Verhees CH, Ettema TJG, van der Saar S, Imamura H, Matsuzawa H, van der Oost J, de Vos WM. ''Identification and molecular characterization of a novel type of α-galactosidase from Pyrococcus furiosus.'' Biocatal Biotransform 2003; 21(4-5) 243-52. ([http://dx.doi.org/10.1080/10242420310001614342 DOI: 10.1080/10242420310001614342])<br />
#Dickmanns2006 pmid=16510973<br />
#Santos2011 pmid=21104698<br />
#Knapp1995 pmid=8749857<br />
#Erra-Pujada1999 pmid=10322035<br />
#Lupas1994 pmid=8113161<br />
#Mizuno2004 pmid=14660574<br />
#Zona2005 Zona R, Janecek S. ''Relationships between SLH motifs from different glycoside hydrolase families.'' Biologia 2005; 60(Suppl. 16): 115-21. ([http://biologia.savba.sk/Suppl_16/Zona_R.pdf PDF])<br />
#Dong1997 pmid=9293009<br />
#Janecek1998 pmid=9721603<br />
#Matsuura1984 pmid=6609921<br />
#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])<br />
#vandenElsen2001 pmid=11406577<br />
</biblio><br />
<br />
[[Category:Glycoside Hydrolase Families|GH057]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_57&diff=17804Glycoside Hydrolase Family 572024-02-05T11:23:30Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
* [[Responsible Curator]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}}<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH57'''<br />
|-<br />
|'''Clan'''<br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH57.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Substrate specificities ==<br />
[[Glycoside hydrolase]] family 57 was established in 1996 <cite>Henrissat1996</cite> based on the existence of the sequences of two “α-amylases” that were dissimilar to typical family [[GH13]] α-amylases <cite>MacGregor2001</cite>. The two were the heat-stable eubacterial amylase from ''Dictyoglomus thermophilum'' known from 1988 <cite>Fukusumi1988</cite> and the extremely thermostable archaeal amylase from ''Pyrococcus furiosus'' determined in 1993 <cite>Laderman1993a</cite>.<br />
<br />
The family has expanded mainly due to the results of genome sequencing projects. More than a thousand of members are known <cite>Cantarel2009,Lombard2014</cite>, all from prokaryotes (with ~1:4 ratio for Archaea:Bacteria) <cite>Blesak2012</cite>. The enzyme specificities of family GH57 includes α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]), α-galactosidase (EC [{{EClink}}3.2.1.22 3.2.1.22]), amylopullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]), branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]) and 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]).<br />
<br />
An archaeal GH57 amylopullulanase from ''Staphylothermus marinus'' has been described exhibiting also the activity of cyclodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]) <cite>Li2013</cite>. Based on a preliminary observation that the PF0870 protein encoded in the ''Pyrococcus furiosus'' genome produced maltose <cite>Comfort2008</cite>, a group of GH57 members with proposed specificity of maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]) was predicted <cite>Blesak2013</cite> together with another group of non-specified amylases following the partial characterization of an amylolytic enzyme from an uncultured bacterium <cite>Wang2011</cite>. The maltogenic specificity (or maltose-forming amylase) has already been definitively confirmed by both biochemical <cite>Jung2014,Jeon2014</cite> and structural <cite>Park2014</cite> studies. The family GH57 contains further a group of probably non-enzymatic members, i.e. the so-called α-amylase-like proteins having a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
<br />
It is worth mentioning that the two founding members, i.e. the “α-amylases” from ''Dictyoglomus thermophilum'' and ''Pyrococcus furiosus'' are 4-α-glucanotransferases; the former was proven to have transglycosylating activity <cite>Nakajima2004</cite>, whereas the latter was already known to exhibit also the 4-α-glucanotransferase activity <cite>Laderman1993b</cite>.<br />
<br />
A detailed in silico prediction study has indicated a close relatedness of family GH57 to the family GH119 concerning catalytic domain fold, catalytic machinery and conserved sequence regions <cite>Janecek2012</cite>. This original prediction has recently been updated <cite>Polacek2023</cite> and finally confirmed by experimental characterization of the <br />
<br />
== Kinetics and Mechanism ==<br />
A direct evidence for the stereochemical outcome of the enzyme-catalyzed reaction has been presented for the branching enzyme from ''Thermus thermophilus'' <cite>Palomo2011</cite> by the NMR analysis of reaction products. The previous observation of a trapped covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> was also a strong evidence that the GH57 enzymes operate with [[retaining|retention]] of anomeric configuration through a [[classical Koshland retaining mechanism]] with retention of anomeric configuration. The X-ray structure of the 4-α-glucanotransferase from ''Thermococcus litoralis'' revealed average distances of 6.72 Å and 6.97 Å between the [[catalytic nucleophile]] (Glu123) and [[general acid/base]] (Asp214) in the free and acarbose-bound forms of the enzyme, respectively, which also supports a retaining mechanism for this family <cite>Imamura2003</cite> (see also <cite>Davies1995</cite>).<br />
<br />
Detailed kinetic studies have been performed on several GH57 enzymes, including the 4-α-glucanotransferases from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> and ''Pyrococcus furiosus'' <cite>Tang2006</cite>, amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>, and branching enzymes from ''Thermococcus kodakaraensis'' <cite>Murakami2006</cite> and ''Thermus thermophilus'' <cite>Palomo2011</cite>.<br />
<br />
== Catalytic Residues ==<br />
The sequences of GH57 members are very diverse. Some sequences are shorter than 400 residues whereas others are longer than 1,500 residues <cite>Janecek2005</cite>. This complicated early efforts to align the GH57 sequences using standard alignment methods. A detailed bioinformatics study by Zona ''et al.'' <cite>Zona2004</cite> focused on all available GH57 sequences at that time and identified five conserved sequence regions. This study used knowledge of the identity of the [[catalytic nucleophile]] (Glu123) in the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001</cite> together with the three-dimensional structure <cite>Imamura2003</cite> (PDB ID [{{PDBlink}}1k1w 1k1w]) that revealed the [[general acid/base]] residue (Asp214).<br />
<br />
The [[catalytic nucleophile]] (a glutamate) and [[general acid/base]] (an aspartate) are located in the conserved sequence regions 3 and 4, respectively. In addition to assignments in ''Thermococcus litoralis'' 4-α-glucanotransferase discussed above, these residues were identified in the amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>. The [[catalytic nucleophile]] was also identified in the α-galactosidase from ''Pyrococcus furiosus'' although no success was achieved in assigning the [[general acid/base]] <cite>vanLieshout2003</cite>. It should be taken into account that some GH57 members, which are only hypothetical enzymes/proteins without any biochemical characterization, may lack one or even both catalytic residues <cite>Zona2004,Janecek2011</cite>.<br />
<br />
Based on the five identified conserved sequence regions, the residues His13, Glu79, Glu216 and Asp354 together with Trp120, Trp221 and Trp357 (''Thermococcus hydrothermalis'' amylopullulanase numbering) were postulated <cite>Zona2004</cite> as important determinants of the individual GH57 enzyme specificities <cite>Janecek2011,Blesak2012,Blesak2013</cite>. Of these, the Trp221 has already been confirmed to contribute to the transglycosylation activity of 4-α-glucanotransferase since the mutant W229H of the enzyme from ''Pyrococcus furiosus'' exhibited markedly decreased transglycosylation activity in comparison with the wild-type counterpart <cite>Tang2006</cite>.<br />
<br />
== Three-dimensional structures ==<br />
The structure of the catalytic domain adopts a (β/α)7-barrel, i.e. the irregular (β/α)8-barrel called a pseudo TIM-barrel. In the case of the ''Thermococcus litoralis'' 4-α-glucanotransferase <cite>Imamura2003</cite> the catalytic domain is succeeded by a C-terminal non-catalytic domain consisting of only β-strands that adopts a twisted β-sandwich fold. In the three-dimensional structure of the α-amylase AmyC from ''Thermotoga maritima'' <cite>Dickmanns2006</cite> (PDB ID [{{PDBlink}}2b5d 2b5d]) (note that the sequence of this enzyme strongly resemles that of a branching enzyme <cite>Blesak2012</cite>), the corresponding catalytic (β/α)7-barrel is followed by a five-helix domain C, a small helical domain B being protruded out of the catalytic pseudo TIM barrel in the place of the loop 2 (i.e. succeeding the strand β2). This structure was found to be closely similar to that of the GH57 member of unknown function from ''Thermus thermophilus'' (PDB ID [{{PDBlink}}1ufa 1ufa]). Two structures of biochemically characterized branching enzymes were solved and published: one from ''Thermus thermophilus'' <cite>Palomo2011</cite> (PDB ID [{{PDBlink}}3p0b 3p0b]) and the other one from ''Thermococcus kodakaraensis'' <cite>Santos2011</cite> (PDB ID [{{PDBlink}}3n8t 3n8t]). The former study <cite>Palomo2011</cite>, importantly, is the first report to prove that a retaining mechanism is employed in the family GH57. Also, the 3-D structure is available for the maltogenic (maltose-forming) amylase from ''Pyrococcus'' sp. ST04 <cite>Park2014</cite> (PDB ID [{{PDBlink}}4cmr 4cmr]). In all cases, the catalytic glutamic acid and aspartic acid residues are located near the C-terminal ends of the strands β4 and β7 of the barrel, respectively <cite>Imamura2003,Dickmanns2006</cite>. There was also a crystallization report in 1995 on a probable GH57 amylopullulanase from ''Pyrococcus woesei'' <cite>Knapp1995</cite>, but the detailed crystallographic analysis of this protein has not been published.<br />
<br />
It is clear that the C-terminal domain cannot be present in some GH57 members with shorter amino acid sequences, e.g., in the α-galactosidases containing less than 400 residues <cite>vanLieshout2003</cite>. On the other hand, some other GH57 members, especially the extra-long amylopullulanases with more than 1,300 residues <cite>Erra-Pujada1999</cite> have to contain even additional domains. One of them could be a longer version of a typical surface layer homology (SLH) motif <cite>Lupas1994</cite> that was named as the so-called SLH motif-bearing domain in the amylopullulanase from ''Thermococcus hydrothermalis'' <cite>Erra-Pujada1999</cite>. This domain was found also in the [[GH15]] glucodextranase from ''Arthrobacter globiformis'' <cite>Mizuno2004</cite>. Remarkably, within the family GH57, the presence of this SLH motif-bearing domain is restricted only for amylopullulanases <cite>Zona2005</cite>.<br />
<br />
It is also worth mentioning that, especially prior the first three-dimensional structure of a GH57 member was available, there were some efforts to join the family GH57 with the main α-amylase family [[GH13]], i.e. the present clan [GH-H] consisting of the families [[GH13]], [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>. Those efforts were focused mainly on looking for some remote homology at the sequence level only <cite>Dong1997,Janecek1998</cite>. Although both GH57 and GH-H employ the same retaining reaction mechanism <cite>Imamura2003,Matsuura1984</cite> the independence of the family GH57 with regard to GH-H clan is at present based not only on differences in the catalytic domain, but more importantly, on the differences in the catalytic machineries and conserved sequence regions <cite>Zona2004,Janecek2002</cite>. As far as other GH families are concerned, the family [[GH38]] α-mannosidase from ''Drosophila melanogaster'' <cite>vandenElsen2001</cite> was revealed to share some structural similarities within the catalytic domain with the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> indicating an eventuality of originating from a common ancestor.<br />
<br />
== Family Firsts ==<br />
;First sterochemistry determination: The first direct evidence of the retaining reaction stereochemistry by product analysis has been delivered by 1H-NMR analysis of the product mixture that confirmed the α-anomeric configuration of the α-1,6-glucosidic bond formed after the incubation of ''Thermus thermophilus'' branching enzyme with amylose <cite>Palomo2011</cite>. Previously, family GH57 enzymes have been indicated to be retaining by trapping of a covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> and a 6.7 Å distance between the catalytic nucleophile and acid/base <cite>Imamura2003</cite>, both of which are consistent with a two-step, double-displacement mechanism. <br />
;First amino acid sequence determination: The first amino acid sequence of the family GH57 was that of the heat stable amylase from an anaerobic thermophilic bacterium ''Dictyoglomus thermophilum'' <cite>Fukusumi1988</cite>. This "α-amylase" was later characterized as 4-α-glucanotransferase <cite>Nakajima2004</cite>. In fact, the family contains many α-amylase-like proteins, i.e. those that exhibit a clear sequence homology with α-amylases, but possess a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
;First conserved sequence regions determination: The five sequence stretches characteristic as conserved regions for the family GH57 were first determined by the bioinformatics study by Zona et al. (2004) <cite>Zona2004</cite>.<br />
;First [[catalytic nucleophile]] identification: The catalytic nucleophile was fist identified by Imamura et al. (2001) <cite>Imamura2001</cite> as Glu123 in the 4-α-glucanotransferase from ''Thermococcus litoralis'' using the 3-ketobutylidene-β-2-chloro-4-nitrophenyl maltopentaoside as a donor.<br />
;First [[general acid/base]] residue identification: Asp214 of the 4-α-glucanotransferase from ''Thermococcus litoralis'' as indicated by the X-ray crystallography and supported by site-directed mutagenesis <cite>Imamura2003</cite> since the D214N mutant exhibited a 10,000-fold decrease of specific activity in comparison with the wild-type enzyme.<br />
;First 3-D structure: The first 3-D structure of a GH57 member was that of the 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2003</cite>.<br />
<br />
== References ==<br />
<biblio><br />
#Henrissat1996 pmid=8687420<br />
#MacGregor2001 pmid=11257505<br />
#Fukusumi1988 pmid=2453362<br />
#Laderman1993a pmid=8226990<br />
#Cantarel2009 pmid=18838391<br />
#Lombard2014 pmid=24270786<br />
#Blesak2012 pmid=22527043<br />
#Li2013 pmid=23001056<br />
#Comfort2008 pmid=18156337<br />
#Blesak2013 pmid=24109595<br />
#Wang2011 pmid=21455739<br />
#Jung2014 pmid=23884203<br />
#Jeon2014 pmid=24835094<br />
#Park2014 pmid=24914977<br />
#Janecek2011 pmid=21786160<br />
#Nakajima2004 pmid=15564678<br />
#Laderman1993b pmid=8226989<br />
#Janecek2012 pmid=22819817<br />
#Palomo2011 pmid=21097495<br />
#Imamura2003 pmid=12618437<br />
#Imamura2001 pmid=11591160<br />
#Davies1995 pmid=8535779<br />
#Tang2006 pmid=17035108<br />
#Zona2004 pmid=15233783<br />
#Kang2005 pmid=15599521<br />
#Murakami2006 pmid=16885460<br />
#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16) 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])<br />
#vanLieshout2003 van Lieshout JFT, Verhees CH, Ettema TJG, van der Saar S, Imamura H, Matsuzawa H, van der Oost J, de Vos WM. ''Identification and molecular characterization of a novel type of α-galactosidase from Pyrococcus furiosus.'' Biocatal Biotransform 2003; 21(4-5) 243-52. ([http://dx.doi.org/10.1080/10242420310001614342 DOI: 10.1080/10242420310001614342])<br />
#Dickmanns2006 pmid=16510973<br />
#Santos2011 pmid=21104698<br />
#Knapp1995 pmid=8749857<br />
#Erra-Pujada1999 pmid=10322035<br />
#Lupas1994 pmid=8113161<br />
#Mizuno2004 pmid=14660574<br />
#Zona2005 Zona R, Janecek S. ''Relationships between SLH motifs from different glycoside hydrolase families.'' Biologia 2005; 60(Suppl. 16): 115-21. ([http://biologia.savba.sk/Suppl_16/Zona_R.pdf PDF])<br />
#Dong1997 pmid=9293009<br />
#Janecek1998 pmid=9721603<br />
#Matsuura1984 pmid=6609921<br />
#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])<br />
#vandenElsen2001 pmid=11406577<br />
</biblio><br />
<br />
[[Category:Glycoside Hydrolase Families|GH057]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_57&diff=17803Glycoside Hydrolase Family 572024-02-05T11:18:13Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
* [[Responsible Curator]]: [[User:Stefan Janecek|Stefan Janecek]]<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}}<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH57'''<br />
|-<br />
|'''Clan'''<br />
|GH-S<br />
|-<br />
|'''Mechanism'''<br />
|retaining<br />
|-<br />
|'''Active site residues'''<br />
|known<br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}GH57.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Substrate specificities ==<br />
[[Glycoside hydrolase]] family 57 was established in 1996 <cite>Henrissat1996</cite> based on the existence of the sequences of two “α-amylases” that were dissimilar to typical family [[GH13]] α-amylases <cite>MacGregor2001</cite>. The two were the heat-stable eubacterial amylase from ''Dictyoglomus thermophilum'' known from 1988 <cite>Fukusumi1988</cite> and the extremely thermostable archaeal amylase from ''Pyrococcus furiosus'' determined in 1993 <cite>Laderman1993a</cite>.<br />
<br />
The family has expanded mainly due to the results of genome sequencing projects. More than a thousand of members are known <cite>Cantarel2009,Lombard2014</cite>, all from prokaryotes (with ~1:4 ratio for Archaea:Bacteria) <cite>Blesak2012</cite>. The enzyme specificities of family GH57 includes α-amylase (EC [{{EClink}}3.2.1.1 3.2.1.1]), α-galactosidase (EC [{{EClink}}3.2.1.22 3.2.1.22]), amylopullulanase (EC [{{EClink}}3.2.1.41 3.2.1.41]), branching enzyme (EC [{{EClink}}2.4.1.18 2.4.1.18]) and 4-α-glucanotransferase (EC [{{EClink}}2.4.1.25 2.4.1.25]).<br />
<br />
An archaeal GH57 amylopullulanase from ''Staphylothermus marinus'' has been described exhibiting also the activity of cyclodextrinase (EC [{{EClink}}3.2.1.54 3.2.1.54]) <cite>Li2013</cite>. Based on a preliminary observation that the PF0870 protein encoded in the ''Pyrococcus furiosus'' genome produced maltose <cite>Comfort2008</cite>, a group of GH57 members with proposed specificity of maltogenic amylase (EC [{{EClink}}3.2.1.133 3.2.1.133]) was predicted <cite>Blesak2013</cite> together with another group of non-specified amylases following the partial characterization of an amylolytic enzyme from an uncultured bacterium <cite>Wang2011</cite>. The maltogenic specificity (or maltose-forming amylase) has already been definitively confirmed by both biochemical <cite>Jung2014,Jeon2014</cite> and structural <cite>Park2014</cite> studies. The family GH57 contains further a group of probably non-enzymatic members, i.e. the so-called α-amylase-like proteins having a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
<br />
It is worth mentioning that the two founding members, i.e. the “α-amylases” from ''Dictyoglomus thermophilum'' and ''Pyrococcus furiosus'' are 4-α-glucanotransferases; the former was proven to have transglycosylating activity <cite>Nakajima2004</cite>, whereas the latter was already known to exhibit also the 4-α-glucanotransferase activity <cite>Laderman1993b</cite>.<br />
<br />
A detailed in silico study has indicated a close relatedness of family GH57 to the family GH119 concerning catalytic domain fold, catalytic machinery and conserved sequence regions <cite>Janecek2012</cite>.<br />
<br />
== Kinetics and Mechanism ==<br />
A direct evidence for the stereochemical outcome of the enzyme-catalyzed reaction has been presented for the branching enzyme from ''Thermus thermophilus'' <cite>Palomo2011</cite> by the NMR analysis of reaction products. The previous observation of a trapped covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> was also a strong evidence that the GH57 enzymes operate with [[retaining|retention]] of anomeric configuration through a [[classical Koshland retaining mechanism]] with retention of anomeric configuration. The X-ray structure of the 4-α-glucanotransferase from ''Thermococcus litoralis'' revealed average distances of 6.72 Å and 6.97 Å between the [[catalytic nucleophile]] (Glu123) and [[general acid/base]] (Asp214) in the free and acarbose-bound forms of the enzyme, respectively, which also supports a retaining mechanism for this family <cite>Imamura2003</cite> (see also <cite>Davies1995</cite>).<br />
<br />
Detailed kinetic studies have been performed on several GH57 enzymes, including the 4-α-glucanotransferases from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> and ''Pyrococcus furiosus'' <cite>Tang2006</cite>, amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>, and branching enzymes from ''Thermococcus kodakaraensis'' <cite>Murakami2006</cite> and ''Thermus thermophilus'' <cite>Palomo2011</cite>.<br />
<br />
== Catalytic Residues ==<br />
The sequences of GH57 members are very diverse. Some sequences are shorter than 400 residues whereas others are longer than 1,500 residues <cite>Janecek2005</cite>. This complicated early efforts to align the GH57 sequences using standard alignment methods. A detailed bioinformatics study by Zona ''et al.'' <cite>Zona2004</cite> focused on all available GH57 sequences at that time and identified five conserved sequence regions. This study used knowledge of the identity of the [[catalytic nucleophile]] (Glu123) in the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001</cite> together with the three-dimensional structure <cite>Imamura2003</cite> (PDB ID [{{PDBlink}}1k1w 1k1w]) that revealed the [[general acid/base]] residue (Asp214).<br />
<br />
The [[catalytic nucleophile]] (a glutamate) and [[general acid/base]] (an aspartate) are located in the conserved sequence regions 3 and 4, respectively. In addition to assignments in ''Thermococcus litoralis'' 4-α-glucanotransferase discussed above, these residues were identified in the amylopullulanases from ''Thermococcus hydrothermalis'' <cite>Zona2004</cite> and ''Pyrococcus furiosus'' <cite>Kang2005</cite>. The [[catalytic nucleophile]] was also identified in the α-galactosidase from ''Pyrococcus furiosus'' although no success was achieved in assigning the [[general acid/base]] <cite>vanLieshout2003</cite>. It should be taken into account that some GH57 members, which are only hypothetical enzymes/proteins without any biochemical characterization, may lack one or even both catalytic residues <cite>Zona2004,Janecek2011</cite>.<br />
<br />
Based on the five identified conserved sequence regions, the residues His13, Glu79, Glu216 and Asp354 together with Trp120, Trp221 and Trp357 (''Thermococcus hydrothermalis'' amylopullulanase numbering) were postulated <cite>Zona2004</cite> as important determinants of the individual GH57 enzyme specificities <cite>Janecek2011,Blesak2012,Blesak2013</cite>. Of these, the Trp221 has already been confirmed to contribute to the transglycosylation activity of 4-α-glucanotransferase since the mutant W229H of the enzyme from ''Pyrococcus furiosus'' exhibited markedly decreased transglycosylation activity in comparison with the wild-type counterpart <cite>Tang2006</cite>.<br />
<br />
== Three-dimensional structures ==<br />
The structure of the catalytic domain adopts a (β/α)7-barrel, i.e. the irregular (β/α)8-barrel called a pseudo TIM-barrel. In the case of the ''Thermococcus litoralis'' 4-α-glucanotransferase <cite>Imamura2003</cite> the catalytic domain is succeeded by a C-terminal non-catalytic domain consisting of only β-strands that adopts a twisted β-sandwich fold. In the three-dimensional structure of the α-amylase AmyC from ''Thermotoga maritima'' <cite>Dickmanns2006</cite> (PDB ID [{{PDBlink}}2b5d 2b5d]) (note that the sequence of this enzyme strongly resemles that of a branching enzyme <cite>Blesak2012</cite>), the corresponding catalytic (β/α)7-barrel is followed by a five-helix domain C, a small helical domain B being protruded out of the catalytic pseudo TIM barrel in the place of the loop 2 (i.e. succeeding the strand β2). This structure was found to be closely similar to that of the GH57 member of unknown function from ''Thermus thermophilus'' (PDB ID [{{PDBlink}}1ufa 1ufa]). Two structures of biochemically characterized branching enzymes were solved and published: one from ''Thermus thermophilus'' <cite>Palomo2011</cite> (PDB ID [{{PDBlink}}3p0b 3p0b]) and the other one from ''Thermococcus kodakaraensis'' <cite>Santos2011</cite> (PDB ID [{{PDBlink}}3n8t 3n8t]). The former study <cite>Palomo2011</cite>, importantly, is the first report to prove that a retaining mechanism is employed in the family GH57. Also, the 3-D structure is available for the maltogenic (maltose-forming) amylase from ''Pyrococcus'' sp. ST04 <cite>Park2014</cite> (PDB ID [{{PDBlink}}4cmr 4cmr]). In all cases, the catalytic glutamic acid and aspartic acid residues are located near the C-terminal ends of the strands β4 and β7 of the barrel, respectively <cite>Imamura2003,Dickmanns2006</cite>. There was also a crystallization report in 1995 on a probable GH57 amylopullulanase from ''Pyrococcus woesei'' <cite>Knapp1995</cite>, but the detailed crystallographic analysis of this protein has not been published.<br />
<br />
It is clear that the C-terminal domain cannot be present in some GH57 members with shorter amino acid sequences, e.g., in the α-galactosidases containing less than 400 residues <cite>vanLieshout2003</cite>. On the other hand, some other GH57 members, especially the extra-long amylopullulanases with more than 1,300 residues <cite>Erra-Pujada1999</cite> have to contain even additional domains. One of them could be a longer version of a typical surface layer homology (SLH) motif <cite>Lupas1994</cite> that was named as the so-called SLH motif-bearing domain in the amylopullulanase from ''Thermococcus hydrothermalis'' <cite>Erra-Pujada1999</cite>. This domain was found also in the [[GH15]] glucodextranase from ''Arthrobacter globiformis'' <cite>Mizuno2004</cite>. Remarkably, within the family GH57, the presence of this SLH motif-bearing domain is restricted only for amylopullulanases <cite>Zona2005</cite>.<br />
<br />
It is also worth mentioning that, especially prior the first three-dimensional structure of a GH57 member was available, there were some efforts to join the family GH57 with the main α-amylase family [[GH13]], i.e. the present clan [GH-H] consisting of the families [[GH13]], [[GH70]] and [[GH77]] <cite>MacGregor2001</cite>. Those efforts were focused mainly on looking for some remote homology at the sequence level only <cite>Dong1997,Janecek1998</cite>. Although both GH57 and GH-H employ the same retaining reaction mechanism <cite>Imamura2003,Matsuura1984</cite> the independence of the family GH57 with regard to GH-H clan is at present based not only on differences in the catalytic domain, but more importantly, on the differences in the catalytic machineries and conserved sequence regions <cite>Zona2004,Janecek2002</cite>. As far as other GH families are concerned, the family [[GH38]] α-mannosidase from ''Drosophila melanogaster'' <cite>vandenElsen2001</cite> was revealed to share some structural similarities within the catalytic domain with the GH57 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2001,Imamura2003</cite> indicating an eventuality of originating from a common ancestor.<br />
<br />
== Family Firsts ==<br />
;First sterochemistry determination: The first direct evidence of the retaining reaction stereochemistry by product analysis has been delivered by 1H-NMR analysis of the product mixture that confirmed the α-anomeric configuration of the α-1,6-glucosidic bond formed after the incubation of ''Thermus thermophilus'' branching enzyme with amylose <cite>Palomo2011</cite>. Previously, family GH57 enzymes have been indicated to be retaining by trapping of a covalent glycosyl-enzyme intermediate <cite>Imamura2001</cite> and a 6.7 Å distance between the catalytic nucleophile and acid/base <cite>Imamura2003</cite>, both of which are consistent with a two-step, double-displacement mechanism. <br />
;First amino acid sequence determination: The first amino acid sequence of the family GH57 was that of the heat stable amylase from an anaerobic thermophilic bacterium ''Dictyoglomus thermophilum'' <cite>Fukusumi1988</cite>. This "α-amylase" was later characterized as 4-α-glucanotransferase <cite>Nakajima2004</cite>. In fact, the family contains many α-amylase-like proteins, i.e. those that exhibit a clear sequence homology with α-amylases, but possess a substitution in one or both catalytic residues <cite>Janecek2011</cite>.<br />
;First conserved sequence regions determination: The five sequence stretches characteristic as conserved regions for the family GH57 were first determined by the bioinformatics study by Zona et al. (2004) <cite>Zona2004</cite>.<br />
;First [[catalytic nucleophile]] identification: The catalytic nucleophile was fist identified by Imamura et al. (2001) <cite>Imamura2001</cite> as Glu123 in the 4-α-glucanotransferase from ''Thermococcus litoralis'' using the 3-ketobutylidene-β-2-chloro-4-nitrophenyl maltopentaoside as a donor.<br />
;First [[general acid/base]] residue identification: Asp214 of the 4-α-glucanotransferase from ''Thermococcus litoralis'' as indicated by the X-ray crystallography and supported by site-directed mutagenesis <cite>Imamura2003</cite> since the D214N mutant exhibited a 10,000-fold decrease of specific activity in comparison with the wild-type enzyme.<br />
;First 3-D structure: The first 3-D structure of a GH57 member was that of the 4-α-glucanotransferase from ''Thermococcus litoralis'' <cite>Imamura2003</cite>.<br />
<br />
== References ==<br />
<biblio><br />
#Henrissat1996 pmid=8687420<br />
#MacGregor2001 pmid=11257505<br />
#Fukusumi1988 pmid=2453362<br />
#Laderman1993a pmid=8226990<br />
#Cantarel2009 pmid=18838391<br />
#Lombard2014 pmid=24270786<br />
#Blesak2012 pmid=22527043<br />
#Li2013 pmid=23001056<br />
#Comfort2008 pmid=18156337<br />
#Blesak2013 pmid=24109595<br />
#Wang2011 pmid=21455739<br />
#Jung2014 pmid=23884203<br />
#Jeon2014 pmid=24835094<br />
#Park2014 pmid=24914977<br />
#Janecek2011 pmid=21786160<br />
#Nakajima2004 pmid=15564678<br />
#Laderman1993b pmid=8226989<br />
#Janecek2012 pmid=22819817<br />
#Palomo2011 pmid=21097495<br />
#Imamura2003 pmid=12618437<br />
#Imamura2001 pmid=11591160<br />
#Davies1995 pmid=8535779<br />
#Tang2006 pmid=17035108<br />
#Zona2004 pmid=15233783<br />
#Kang2005 pmid=15599521<br />
#Murakami2006 pmid=16885460<br />
#Janecek2005 Janecek S ''Amylolytic families of glycoside hydrolases: focus on the family GH-57.'' Biologia 2005; 60(Suppl. 16) 177-84. ([http://biologia.savba.sk/Suppl_16/Janecek_S.pdf PDF])<br />
#vanLieshout2003 van Lieshout JFT, Verhees CH, Ettema TJG, van der Saar S, Imamura H, Matsuzawa H, van der Oost J, de Vos WM. ''Identification and molecular characterization of a novel type of α-galactosidase from Pyrococcus furiosus.'' Biocatal Biotransform 2003; 21(4-5) 243-52. ([http://dx.doi.org/10.1080/10242420310001614342 DOI: 10.1080/10242420310001614342])<br />
#Dickmanns2006 pmid=16510973<br />
#Santos2011 pmid=21104698<br />
#Knapp1995 pmid=8749857<br />
#Erra-Pujada1999 pmid=10322035<br />
#Lupas1994 pmid=8113161<br />
#Mizuno2004 pmid=14660574<br />
#Zona2005 Zona R, Janecek S. ''Relationships between SLH motifs from different glycoside hydrolase families.'' Biologia 2005; 60(Suppl. 16): 115-21. ([http://biologia.savba.sk/Suppl_16/Zona_R.pdf PDF])<br />
#Dong1997 pmid=9293009<br />
#Janecek1998 pmid=9721603<br />
#Matsuura1984 pmid=6609921<br />
#Janecek2002 Janecek S. ''How many conserved sequence regions are there in the α-amylase family?'' Biologia 2002; 57(Suppl. 11): 29-41. ([http://biologia.savba.sk/Suppl_11/Janecek.pdf PDF])<br />
#vandenElsen2001 pmid=11406577<br />
</biblio><br />
<br />
[[Category:Glycoside Hydrolase Families|GH057]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=13659User:Stefan Janecek2019-04-27T08:59:13Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as families [[GH57]] with [[GH119]], and eventually also [[GH126]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve fifteen [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]], [[CBM69]], [[CBM74]], [[CBM82]] and [[CBM83]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs]; for the most recent one, being held in autumn 2019, please click: [http://imb.savba.sk/~janecek/Alamys/Alamy_7/ ALAMY_7].<br />
<br />
He is also founder and the Editor-in-Chief of the brand new, open access journal [http://www.degruyter.com/view/j/amylase Amylase].<br />
<br />
He serves as the Associate Editor of the journal [http://www.springer.com/chemistry/biotechnology/journal/13205 3Biotech] and Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology, too.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=11752User:Stefan Janecek2017-09-19T12:03:28Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as the families [[GH57]] and [[GH119]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve thirteen [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]], [[CBM69]] and [[CBM74]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs].<br />
<br />
He is also founder and the Editor-in-Chief of the brand new, open access journal [http://www.degruyter.com/view/j/amylase Amylase].<br />
<br />
He serves as the Associate Editor of the journal [http://www.springer.com/chemistry/biotechnology/journal/13205 3Biotech] and Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology, too.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=11204User:Stefan Janecek2016-10-20T07:44:03Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as the families [[GH57]] and [[GH119]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve thirteen [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]], [[CBM69]] and [[CBM74]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs].<br />
<br />
He is also founder and the Editor-in-Chief of the brand new, open access journal [http://www.degruyter.com/view/j/amylase Amylase].<br />
<br />
He serves as the Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology, too.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=11203User:Stefan Janecek2016-10-20T07:43:09Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as the families [[GH57]] and [[GH119]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve thirteen [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]], [[CBM69]] and [[CBM74]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs].<br />
<br />
He is also founder and the Editor-in-Chief of the brand new, open access journal [https://www.degruyter.com/view/j/amylase Amylase].<br />
<br />
He serves as the Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology, too.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=11202User:Stefan Janecek2016-10-20T07:41:57Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as the families [[GH57]] and [[GH119]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve thirteen [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]], [[CBM69]] and [[CBM74]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs].<br />
<br />
He is also founder and the Editor-in-Chief of the brand new, open access journal Amylase.<br />
<br />
He serves as the Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology, too.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=11035User:Stefan Janecek2016-02-03T07:31:14Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as the families [[GH57]] and [[GH119]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve twelve [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]] and [[CBM69]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs].<br />
<br />
He is also the Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=User:Stefan_Janecek&diff=10802User:Stefan Janecek2015-07-31T08:31:58Z<p>Stefan Janecek: </p>
<hr />
<div>[[Image:Stefan Janecek.jpg|150px|right]]<br />
<br />
Stefan Janecek is a research scientist at the Institute of Molecular Biology of the Slovak Academy of Sciences, Bratislava, Slovakia and a teacher at the Department of Biology of the Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava, Slovakia. <br />
<br />
He is a group leader heading the [http://imb.savba.sk/~janecek/ Laboratory of Protein Evolution].<br />
<br />
He is most interested in the enzymes and proteins from the alpha-amylase family - the clan GH-H of glycoside hydrolase families [[GH13]], [[GH70]] and [[GH77]] as well as the families [[GH57]] and [[GH119]], especially in their evolution as well as their structure-function and structure-stability relationships. In addition, he is also very interested in bioinformatics studies of starch-binding domains that currently involve ten [http://www.cazy.org/ CAZy] [[Carbohydrate Binding Module Families|CBM families]]: [[CBM20]], [[CBM21]], [[CBM25]], [[CBM26]], [[CBM34]], [[CBM41]], [[CBM45]], [[CBM48]], [[CBM53]], [[CBM58]], [[CBM68]] and [[CBM69]].<br />
<br />
Stefan works as a protein bioinfomatician, being engaged especially in the in silico studies. In his close collaboration with experimentalists, they have three amylolytic enzymes used as experimental models: (i) [[GH13]] alpha-amylase from ''Thermococcus hydrothermalis''; (ii) [[GH57]] amylopullulanase from ''Thermococcus hydrothermalis''; and (iii) [[GH77]] amylomaltase from ''Borrelia burgdorferi''. The experimental work is focused on protein design of these enzymes based on bioinformatics analyses.<br />
<br />
Stefan is founder and main organiser of the international symposia on the alpha-amylase enzyme family - [http://imb.savba.sk/~janecek/Alamys/ ALAMYs].<br />
<br />
He is also the Managing Editor of the journal [http://www.degruyter.com/view/j/biolog Biologia], section Cellular and Molecular Biology.<br />
<br />
[[Category:Contributors|Janecek,Stefan]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10684Carbohydrate Binding Module Family 482015-07-08T19:48:06Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 Koay2010 Meekins2014 Polekhina2005 Katsuya1998 Feese2000 Abad2002 Timmis2005 Leiros2006 Mikami2006 Amodeo2007 Woo2008 Gourlay2009 Turkenburg2009 Pal2010 Song2010 Vander-Kooi2010 Vester-Christensen2010 Noguchi2011 Moeller2012 Okazaki2012 Park2013 Xiao2013 Calabrese2014 Sim2014 Xu2014 Li2015 Moeller2015a Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family [[GH13]] precedes the catalytic TIM-barrel. This is the case of isoamylase <cite>Katsuya1998 Sim2014</cite>, maltooligosyltrehalohydrolase <cite>Feese2000 Timmis2005 Leiros2006</cite>, branching enzyme <cite>Chaen2012 Abad2002 Pal2010 Noguchi2011 Palomo2009</cite>, debranching enzyme <cite>Woo2008 Song2010</cite>, pullulanase <cite>Mikami2006 Gourlay2009 Turkenburg2009 Xu2014</cite>, limit dextrinase <cite>Vester-Christensen2010 Moeller2012 Moeller2015a Moeller2015b</cite> and a bifunctional α-amylase/cyclomaltodextrinase <cite>Park2013</cite>. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain <cite>Meekins2014 Vander-Kooi2010 Gentry2009</cite>. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule <cite>Koay2010 Polekhina2005 Mobbs2015 Xiao2013 Calabrese2014 Li2015</cite>; the same applies for AMPK’s yeast homologue SNF1 <cite>Amodeo2007</cite>. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis <cite>Peng2014a</cite>. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family CBM48 are most closely related to those from the family [[CBM20]] <cite>Janecek2011</cite> and, in a wider sense, also to those from families [[CBM21]], [[CBM53]] <cite>Machovic2006a Christiansen2009</cite> and the recently established family [[CBM69]] <cite>Peng2014b</cite>.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa <cite>Machovic2006a</cite> and then defined within the CAZy database as an independent CBM family <cite>Machovic2008 Cantarel2009</cite>.<br />
;First Structural Characterization<br />
Based on current knowledge <cite>Janecek2011 Machovic2008 Cantarel2009</cite>, the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa <cite>Katsuya1998</cite>. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK <cite>Polekhina2005</cite>, but it is of note that at that time the family CBM48 was not established <cite>Machovic2006b</cite>. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander-Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_21&diff=10683Carbohydrate Binding Module Family 212015-07-08T19:47:14Z<p>Stefan Janecek: </p>
<hr />
<div>{{CuratorApproved}}<br />
* [[Author]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
* [[Responsible Curator]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM21.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Modules from family CBM21 bind to the α-glucan starch and oligosaccharides derived from starch or related to such oligosaccharides that contain α-1,4-linked glucose and/or α-1,6-linked glucose including maltose through maltoheptaose, β- and γ-cyclodextrins, isomaltotriose and isomaltotetraose <cite>Chou2006 Chu2014 Liu2007 Tung2008</cite>. CBM21 also interacts with amylose and alters its ultrastructure as demonstrated by atomic force microscopy <cite>Jiang2012</cite>. Circular permutation enhanced the affinity for amylose <cite>Stephen2012</cite>. The domain has been described as providing mainly glucoamylase and α-amylase with the ability to bind onto raw-starch (starch granules) <cite>Ashikari1986 Bui1996 Houghton-Larsen2003 Steyn1995 Kang2004</cite>.<br />
<br />
== Structural Features ==<br />
Structures of CBM21 have been determined by NMR and X-ray crystallography both in free and in carbohydrate complexed form. They adopt a common β-sandwich fold and have two binding sites accommodating carbohydrate ligands similarly to other starch binding domains. The binding sites contain aromatic side chains participating in carbohydrate interaction. Initially it was described by modelling using an NMR structure of a CBM20 as template <cite>Chou2006</cite> and thereafter by docking onto the NMR structure determined for CBM21 from the family [[GH15]] ''Rhizopus oryzae'' glucoamylase <cite>Liu2007</cite>. The crystal structure determined for this CBM21 in complex with β-cyclodextrin or maltoheptaose identified W47, Y83 and Y94 interacting at site I and Y32 and F58 at site II for both ligands <cite>Tung2008</cite>. Site I requires ligands with DP > 3 for binding <cite>Chu2014</cite>. A CBM21-like domain was identified in the crystal structure of barley family [[GH13]] limit dextrinase <cite>Moeller2012</cite>.<br />
<br />
== Functionalities == <br />
CBM21s are mainly associated with some fungal glucoamylases and α-amylases of the family [[GH15]] <cite>Ashikari1986 Bui1996 Houghton-Larsen2003</cite> and [[GH13]] <cite>Steyn1995 Kang2004</cite>, respectively. This was confirmed by an exhaustive evolutionary analysis of 85 fungal genomes <cite>Chen2012</cite>. In both cases, i.e. in [[GH15]] glucoamylases and [[GH13]] α-amylases, the CBM21 precedes the catalytic domain <cite>Machovic2005</cite>. The CBM21 is present also as a part of the regulatory subunit of Ser/Thr-specific protein phosphatases that directs the protein phosphatase to glycogen <cite>Bork1998</cite>. Recently, a structural comparison identified an N-terminal CBM21-like domain in the barley [[GH13]] limit dextrinase <cite>Moeller2012</cite>, where it is followed by the module from the family [[CBM48]] succeeded by the catalytic TIM-barrel.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
Family CBM21 was first observed as an N-terminally located domain in glucoamylase from ''Rhizopus oryzae'' <cite>Ashikari1986</cite>. The function was ascribed based on comparison of multiple forms of the glucoamylase <cite>Ashikari1986 Takahashi1982</cite> and amino acid sequence alignment <cite>Tanaka1986</cite>. The CBM21 sequence was revealed as related to that of the starch binding domain of ''Aspergillus niger'' glucoamylase <cite>Svensson1989</cite>, which has been assigned the family [[CBM20]] <cite>Machovic2005 Machovic2006 Christiansen2009</cite>.<br />
;First Structural Characterization<br />
The first CBM21 three-dimensional structure was determined by NMR for the module from the family [[GH15]] glucoamylase from ''Rhizopus oryzae'' <cite>Liu2007</cite>. The first CBM21 complex structures were determined by X-ray crystallography for that domain binding to β-cyclodextrin or maltoheptaose <cite>Tung2008</cite>.<br />
<br />
== Novel Applications ==<br />
The CBM21 from ''Rhizopus oryzae'' glucoamylase has been introduced as a novel affinity purification tag <cite>Lin2009</cite>. <br />
<br />
== References ==<br />
<biblio><br />
#Chou2006 pmid=16509822<br />
#Chu2014 pmid=24108499<br />
#Liu2007 pmid=17117925<br />
#Tung2008 pmid=18588504<br />
#Jiang2012 pmid=22815939<br />
#Stephen2012 pmid=23226294<br />
#Ashikari1986 Ashikari T, Nakamura N, Tanaka Y, Kiuchi N, Shibano Y, Tanaka T, Amachi T, and Yoshizumi H. “Rhizopus raw-starch-degrading glucoamylase: its cloning and expression in yeast.” Agric. Biol. Chem. 1986; 50: 957-64.<br />
#Bui1996 pmid=8920185<br />
#Houghton-Larsen2003 pmid=12883866<br />
#Steyn1995 pmid=8529895<br />
#Kang2004 pmid=15043869<br />
#Moeller2012 pmid=22949184<br />
#Chen2012 pmid=23166747<br />
#Machovic2005 pmid=16262690<br />
#Bork1998 pmid=9500672<br />
#Takahashi1982 pmid=6818228<br />
#Tanaka1986 Tanaka Y, Ashikari T, Nakamura N, Kiuchi N, Shibano Y, Amachi T, and Yoshizumi H. Comparison of amino acid sequences of three glucoamylases and their structure-function relationships. Agric. Biol. Chem. 1986; 50: 965-9.<br />
#Svensson1989 pmid=2481445<br />
#Machovic2006 pmid=17013558<br />
#Christiansen2009 pmid=19682075<br />
#Lin2009 pmid=19297701 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM021]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_21&diff=10682Carbohydrate Binding Module Family 212015-07-07T15:40:03Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
* [[Responsible Curator]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM21.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Modules from family CBM21 bind to the α-glucan starch and oligosaccharides derived from starch or related to such oligosaccharides that contain α-1,4-linked glucose and/or α-1,6-linked glucose including maltose through maltoheptaose, β- and γ-cyclodextrins, isomaltotriose and isomaltotetraose <cite>Chou2006 Chu2014 Liu2007 Tung2008</cite>. CBM21 also interacts with amylose and alters its ultrastructure as demonstrated by atomic force microscopy <cite>Jiang2012</cite>. Circular permutation enhanced the affinity for amylose <cite>Stephen2012</cite>. The domain has been described as providing mainly glucoamylase and α-amylase with the ability to bind onto raw-starch (starch granules) <cite>Ashikari1986 Bui1996 Houghton-Larsen2003 Steyn1995 Kang2004</cite>.<br />
<br />
== Structural Features ==<br />
Structures of CBM21 have been determined by NMR and X-ray crystallography both in free and in carbohydrate complexed form. They adopt a common β-sandwich fold and have two binding sites accommodating carbohydrate ligands similarly to other starch binding domains. The binding sites contain aromatic side chains participating in carbohydrate interaction. Initially it was described by modelling using an NMR structure of a CBM20 as template <cite>Chou2006</cite> and thereafter by docking onto the NMR structure determined for CBM21 from the family [[GH15]] ''Rhizopus oryzae'' glucoamylase <cite>Liu2007</cite>. The crystal structure determined for this CBM21 in complex with β-cyclodextrin or maltoheptaose identified W47, Y83 and Y94 interacting at site I and Y32 and F58 at site II for both ligands <cite>Tung2008</cite>. Site I requires ligands with DP > 3 for binding <cite>Chu2014</cite>. A CBM21-like domain was identified in the crystal structure of barley family [[GH13]] limit dextrinase <cite>Moeller2012</cite>.<br />
<br />
== Functionalities == <br />
CBM21s are mainly associated with some fungal glucoamylases and α-amylases of the family [[GH15]] <cite>Ashikari1986 Bui1996 Houghton-Larsen2003</cite> and [[GH13]] <cite>Steyn1995 Kang2004</cite>, respectively. This was confirmed by an exhaustive evolutionary analysis of 85 fungal genomes <cite>Chen2012</cite>. In both cases, i.e. in [[GH15]] glucoamylases and [[GH13]] α-amylases, the CBM21 precedes the catalytic domain <cite>Machovic2005</cite>. The CBM21 is present also as a part of the regulatory subunit of Ser/Thr-specific protein phosphatases that directs the protein phosphatase to glycogen <cite>Bork1998</cite>. Recently, a structural comparison identified an N-terminal CBM21-like domain in the barley [[GH13]] limit dextrinase <cite>Moeller2012</cite>, where it is followed by the module from the family [[CBM48]] succeeded by the catalytic TIM-barrel.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
Family CBM21 was first observed as an N-terminally located domain in glucoamylase from ''Rhizopus oryzae'' <cite>Ashikari1986</cite>. The function was ascribed based on comparison of multiple forms of the glucoamylase <cite>Ashikari1986 Takahashi1982</cite> and amino acid sequence alignment <cite>Tanaka1986</cite>. The CBM21 sequence was revealed as related to that of the starch binding domain of ''Aspergillus niger'' glucoamylase <cite>Svensson1989</cite>, which has been assigned the family [[CBM20]] <cite>Machovic2005 Machovic2006 Christiansen2009</cite>.<br />
;First Structural Characterization<br />
The first CBM21 three-dimensional structure was determined by NMR for the module from the family [[GH15]] glucoamylase from ''Rhizopus oryzae'' <cite>Liu2007</cite>. The first CBM21 complex structures were determined by X-ray crystallography for that domain binding to β-cyclodextrin or maltoheptaose <cite>Tung2008</cite>.<br />
<br />
== Novel Applications ==<br />
The CBM21 from ''Rhizopus oryzae'' glucoamylase has been introduced as a novel affinity purification tag <cite>Lin2009</cite>. <br />
<br />
== References ==<br />
<biblio><br />
#Chou2006 pmid=16509822<br />
#Chu2014 pmid=24108499<br />
#Liu2007 pmid=17117925<br />
#Tung2008 pmid=18588504<br />
#Jiang2012 pmid=22815939<br />
#Stephen2012 pmid=23226294<br />
#Ashikari1986 Ashikari T, Nakamura N, Tanaka Y, Kiuchi N, Shibano Y, Tanaka T, Amachi T, and Yoshizumi H. “Rhizopus raw-starch-degrading glucoamylase: its cloning and expression in yeast.” Agric. Biol. Chem. 1986; 50: 957-64.<br />
#Bui1996 pmid=8920185<br />
#Houghton-Larsen2003 pmid=12883866<br />
#Steyn1995 pmid=8529895<br />
#Kang2004 pmid=15043869<br />
#Moeller2012 pmid=22949184<br />
#Chen2012 pmid=23166747<br />
#Machovic2005 pmid=16262690<br />
#Bork1998 pmid=9500672<br />
#Takahashi1982 pmid=6818228<br />
#Tanaka1986 Tanaka Y, Ashikari T, Nakamura N, Kiuchi N, Shibano Y, Amachi T, and Yoshizumi H. Comparison of amino acid sequences of three glucoamylases and their structure-function relationships. Agric. Biol. Chem. 1986; 50: 965-9.<br />
#Svensson1989 pmid=2481445<br />
#Machovic2006 pmid=17013558<br />
#Christiansen2009 pmid=19682075<br />
#Lin2009 pmid=19297701 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM021]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_21&diff=10678Carbohydrate Binding Module Family 212015-07-07T12:56:27Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
* [[Responsible Curator]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM21.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Modules from family CBM21 bind to the α-glucan starch and oligosaccharides derived from starch or related to such oligosaccharides that contain α-1,4-linked glucose and/or α-1,6-linked glucose including maltose through maltoheptaose, β- and γ-cyclodextrins, isomaltotriose and isomaltotetraose <cite>Chou2006 Chu2014 Liu2007 Tung2008</cite>. CBM21 also interacts with amylose and alters its ultrastructure as demonstrated by atomic force microscopy <cite>Jiang2012</cite>. Circular permutation enhanced the affinity for amylose <cite>Stephen2012</cite>. The domain has been described as providing mainly glucoamylase and α-amylase with the ability to bind onto raw-starch (starch granules) <cite>Ashikari1986 Bui1996 Houghton-Larsen2003 Steyn1995 Kang2004</cite>.<br />
<br />
== Structural Features ==<br />
Structures of CBM21 have been determined by NMR and X-ray crystallography both in free and in carbohydrate complexed form. They adopt a common β-sandwich fold and have two binding sites accommodating carbohydrate ligands similarly to other starch binding domains. The binding sites contain aromatic side chains participating in carbohydrate interaction. Initially it was described by modelling using an NMR structure of a CBM20 as template <cite>Chou2006</cite> and thereafter by docking onto the NMR structure determined for CBM21 from the family [[GH15]] ''Rhizopus oryzae'' glucoamylase <cite>Liu2007</cite>. The crystal structure determined for this CBM21 in complex with β-cyclodextrin or maltoheptaose identified W47, Y83 and Y94 interacting at site I and Y32 and F58 at site II for both ligands <cite>Tung2008</cite>. Site I requires ligands with DP > 3 for binding <cite>Chu2014</cite>. A CBM21-like domain was identified in the crystal structure of barley family [[GH13]] limit dextrinase <cite>Moeller2012</cite>.<br />
<br />
== Functionalities == <br />
CBM21s are mainly associated with some fungal glucoamylases and α-amylases of the family [[GH15]] <cite>Ashikari1986 Bui1996 Houghton-Larsen2003</cite> and [[GH13]] <cite>Steyn1995 Kang2004</cite>, respectively. This was confirmed by an exhaustive evolutionary analysis of 85 fungal genomes <cite>Chen2012</cite>. In both cases, i.e. in [[GH15]] glucoamylases and [[GH13]] α-amylases, the CBM21 precedes the catalytic domain <cite>Machovic2005</cite>. The CBM21 is present also as a part of the regulatory subunit of Ser/Thr-specific protein phosphatases that directs the protein phosphatase to glycogen <cite>Bork1998</cite>. Recently, a structural comparison identified an N-terminal CBM21-like domain in the barley GH13 limit dextrinase <cite>Moeller2012</cite>, where it is followed by the module from the family [[CBM48]] succeeded by the catalytic TIM-barrel.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
Family CBM21 was first observed as an N-terminally located domain in glucoamylase from ''Rhizopus oryzae'' <cite>Ashikari1986</cite>. The function was ascribed based on comparison of multiple forms of the glucoamylase <cite>Ashikari1986 Takahashi1982</cite> and amino acid sequence alignment <cite>Tanaka1986</cite>. The CBM21 sequence was revealed as related to that of the starch binding domain of ''Aspergillus niger'' glucoamylase <cite>Svensson1989</cite>, which has been assigned the family [[CBM20]] <cite>Machovic2005 Machovic2006 Christiansen2009</cite>.<br />
;First Structural Characterization<br />
The first CBM21 three-dimensional structure was determined by NMR for the module from the family [[GH15]] glucoamylase from ''Rhizopus oryzae'' <cite>Liu2007</cite>. The first CBM21 complex structures were determined by X-ray crystallography for that domain binding to β-cyclodextrin or maltoheptaose <cite>Tung2008</cite>.<br />
<br />
== Novel Applications ==<br />
The CBM21 from ''Rhizopus oryzae'' glucoamylase has been introduced as a novel affinity purification tag <cite>Lin2009</cite>. <br />
<br />
== References ==<br />
<biblio><br />
#Chou2006 pmid=16509822<br />
#Chu2014 pmid=24108499<br />
#Liu2007 pmid=17117925<br />
#Tung2008 pmid=18588504<br />
#Jiang2012 pmid=22815939<br />
#Stephen2012 pmid=23226294<br />
#Ashikari1986 Ashikari T, Nakamura N, Tanaka Y, Kiuchi N, Shibano Y, Tanaka T, Amachi T, and Yoshizumi H. “Rhizopus raw-starch-degrading glucoamylase: its cloning and expression in yeast.” Agric. Biol. Chem. 1986; 50: 957-64.<br />
#Bui1996 pmid=8920185<br />
#Houghton-Larsen2003 pmid=12883866<br />
#Steyn1995 pmid=8529895<br />
#Kang2004 pmid=15043869<br />
#Moeller2012 pmid=22949184<br />
#Chen2012 pmid=23166747<br />
#Machovic2005 pmid=16262690<br />
#Bork1998 pmid=9500672<br />
#Takahashi1982 pmid=6818228<br />
#Tanaka1986 Tanaka Y, Ashikari T, Nakamura N, Kiuchi N, Shibano Y, Amachi T, and Yoshizumi H. Comparison of amino acid sequences of three glucoamylases and their structure-function relationships. Agric. Biol. Chem. 1986; 50: 965-9.<br />
#Svensson1989 pmid=2481445<br />
#Machovic2006 pmid=17013558<br />
#Christiansen2009 pmid=19682075<br />
#Lin2009 pmid=19297701 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM021]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_21&diff=10677Carbohydrate Binding Module Family 212015-07-07T12:54:58Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
* [[Responsible Curator]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM21.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Modules from family CBM21 bind to the α-glucan starch and oligosaccharides derived from starch or related to such oligosaccharides that contain α-1,4-linked glucose and/or α-1,6-linked glucose including maltose through maltoheptaose, β- and γ-cyclodextrins, isomaltotriose and isomaltotetraose <cite>Chou2006 Chu2014 Liu2007 Tung2008</cite>. CBM21 also interacts with amylose and alters its ultrastructure as demonstrated by atomic force microscopy <cite>Jiang2012</cite>. Circular permutation enhanced the affinity for amylose <cite>Stephen2012</cite>. The domain has been described as providing mainly glucoamylase and α-amylase with the ability to bind onto raw-starch (starch granules) <cite>Ashikari1986 Bui1996 Houghton-Larsen2003 Steyn1995 Kang2004</cite>.<br />
<br />
== Structural Features ==<br />
Structures of CBM21 have been determined by NMR and X-ray crystallography both in free and in carbohydrate complexed form. They adopt a common β-sandwich fold and have two binding sites accommodating carbohydrate ligands similarly to other starch binding domains. The binding sites contain aromatic side chains participating in carbohydrate interaction. Initially it was described by modelling using an NMR structure of a CBM20 as template <cite>Chou2006</cite> and thereafter by docking onto the NMR structure determined for CBM21 from the family [[GH15]] ''Rhizopus oryzae'' glucoamylase <cite>Liu2007</cite>. The crystal structure determined for this CBM21 in complex with β-cyclodextrin or maltoheptaose identified W47, Y83 and Y94 interacting at site I and Y32 and F58 at site II for both ligands <cite>Tung2008</cite>. Site I requires ligands with DP > 3 for binding <cite>Chu2014</cite>. A CBM21-like domain was identified in the crystal structure of barley family [[GH13]] limit dextrinase <cite>Møller2012</cite>.<br />
<br />
== Functionalities == <br />
CBM21s are mainly associated with some fungal glucoamylases and α-amylases of the family [[GH15]] <cite>Ashikari1986 Bui1996 Houghton-Larsen2003</cite> and [[GH13]] <cite>Steyn1995 Kang2004</cite>, respectively. This was confirmed by an exhaustive evolutionary analysis of 85 fungal genomes <cite>Chen2012</cite>. In both cases, i.e. in [[GH15]] glucoamylases and [[GH13]] α-amylases, the CBM21 precedes the catalytic domain <cite>Machovic2005</cite>. The CBM21 is present also as a part of the regulatory subunit of Ser/Thr-specific protein phosphatases that directs the protein phosphatase to glycogen <cite>Bork1998</cite>. Recently, a structural comparison identified an N-terminal CBM21-like domain in the barley GH13 limit dextrinase <cite>Møller2012</cite>, where it is followed by the module from the family [[CBM48]] succeeded by the catalytic TIM-barrel.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
Family CBM21 was first observed as an N-terminally located domain in glucoamylase from ''Rhizopus oryzae'' <cite>Ashikari1986</cite>. The function was ascribed based on comparison of multiple forms of the glucoamylase <cite>Ashikari1986 Takahashi1982</cite> and amino acid sequence alignment <cite>Tanaka1986</cite>. The CBM21 sequence was revealed as related to that of the starch binding domain of ''Aspergillus niger'' glucoamylase <cite>Svensson1989</cite>, which has been assigned the family [[CBM20]] <cite>Machovic2005 Machovic2006 Christiansen2009</cite>.<br />
;First Structural Characterization<br />
The first CBM21 three-dimensional structure was determined by NMR for the module from the family [[GH15]] glucoamylase from ''Rhizopus oryzae'' <cite>Liu2007</cite>. The first CBM21 complex structures were determined by X-ray crystallography for that domain binding to β-cyclodextrin or maltoheptaose <cite>Tung2008</cite>.<br />
<br />
== Novel Applications ==<br />
The CBM21 from ''Rhizopus oryzae'' glucoamylase has been introduced as a novel affinity purification tag <cite>Lin2009</cite>. <br />
<br />
== References ==<br />
<biblio><br />
#Chou2006 pmid=16509822<br />
#Chu2014 pmid=24108499<br />
#Liu2007 pmid=17117925<br />
#Tung2008 pmid=18588504<br />
#Jiang2012 pmid=22815939<br />
#Stephen2012 pmid=23226294<br />
#Ashikari1986 Ashikari T, Nakamura N, Tanaka Y, Kiuchi N, Shibano Y, Tanaka T, Amachi T, and Yoshizumi H. “Rhizopus raw-starch-degrading glucoamylase: its cloning and expression in yeast.” Agric. Biol. Chem. 1986; 50: 957-64.<br />
#Bui1996 pmid=8920185<br />
#Houghton-Larsen2003 pmid=12883866<br />
#Steyn1995 pmid=8529895<br />
#Kang2004 pmid=15043869<br />
#Møller2012 pmid=22949184<br />
#Chen2012 pmid=23166747<br />
#Machovic2005 pmid=16262690<br />
#Bork1998 pmid=9500672<br />
#Takahashi1982 pmid=6818228<br />
#Tanaka1986 Tanaka Y, Ashikari T, Nakamura N, Kiuchi N, Shibano Y, Amachi T, and Yoshizumi H. Comparison of amino acid sequences of three glucoamylases and their structure-function relationships. Agric. Biol. Chem. 1986; 50: 965-9.<br />
#Svensson1989 pmid=2481445<br />
#Machovic2006 pmid=17013558<br />
#Christiansen2009 pmid=19682075<br />
#Lin2009 pmid=19297701 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM021]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_21&diff=10676Carbohydrate Binding Module Family 212015-07-07T12:51:43Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
* [[Responsible Curator]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM21.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Modules from family CBM21 bind to the α-glucan starch and oligosaccharides derived from starch or related to such oligosaccharides that contain α-1,4-linked glucose and/or α-1,6-linked glucose including maltose through maltoheptaose, β- and γ-cyclodextrins, isomaltotriose and isomaltotetraose <cite>Chou2006 Chu2014 Liu2007 Tung2008</cite>. CBM21 also interacts with amylose and alters its ultrastructure as demonstrated by atomic force microscopy <cite>Jiang2012</cite>. Circular permutation enhanced the affinity for amylose <cite>Stephen2012</cite>. The domain has been described as providing mainly glucoamylase and α-amylase with the ability to bind onto raw-starch (starch granules) <cite>Ashikari1986 Bui1996 Houghton-Larsen2003 Steyn1995 Kang2004</cite>.<br />
<br />
== Structural Features ==<br />
Structures of CBM21 have been determined by NMR and X-ray crystallography both in free and in carbohydrate complexed form. They adopt a common β-sandwich fold and have two binding sites accommodating carbohydrate ligands similarly to other starch binding domains. The binding sites contain aromatic side chains participating in carbohydrate interaction. Initially it was described by modelling using an NMR structure of a CBM20 as template <cite>Chou2006</cite> and thereafter by docking onto the NMR structure determined for CBM21 from the family GH15 ''Rhizopus oryzae'' glucoamylase <cite>Liu2007</cite>. The crystal structure determined for this CBM21 in complex with β -cyclodextrin or maltoheptaose identified W47, Y83 and Y94 interacting at site I and Y32 and F58 at site II for both ligands <cite>Tung2008</cite>. Site I requires ligands with DP > 3 for binding <cite>Chu2014</cite>. A CBM21-like domain was identified in the crystal structure of barley family [[GH13]] limit dextrinase <cite>Møller2012</cite>.<br />
<br />
== Functionalities == <br />
CBM21s are mainly associated with some fungal glucoamylases and α-amylases of the family [[GH15]] <cite>Ashikari1986 Bui1996 Houghton-Larsen2003</cite> and [[GH13]] <cite>Steyn1995 Kang2004</cite>, respectively. This was confirmed by an exhaustive evolutionary analysis of 85 fungal genomes <cite>Chen2012</cite>. In both cases, i.e. in [[GH15]] glucoamylases and [[GH13]] α-amylases, the CBM21 precedes the catalytic domain <cite>Machovic2005</cite>. The CBM21 is present also as a part of the regulatory subunit of Ser/Thr-specific protein phosphatases that directs the protein phosphatase to glycogen <cite>Bork1998</cite>. Recently, a structural comparison identified an N-terminal CBM21-like domain in the barley GH13 limit dextrinase <cite>Møller2012</cite>, where it is followed by the module from the family [[CBM48]] succeeded by the catalytic TIM-barrel.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
Family CBM21 was first observed as an N-terminally located domain in glucoamylase from ''Rhizopus oryzae'' <cite>Ashikari1986</cite>. The function was ascribed based on comparison of multiple forms of the glucoamylase <cite>Ashikari1986 Takahashi1982</cite> and amino acid sequence alignment <cite>Tanaka1986</cite>. The CBM21 sequence was revealed as related to that of the starch binding domain of ''Aspergillus niger'' glucoamylase <cite>Svensson1989</cite>, which has been assigned the family [[CBM20]] <cite>Machovic2005 Machovic2006 Christiansen2009</cite>.<br />
;First Structural Characterization<br />
The first CBM21 three-dimensional structure was determined by NMR for the module from the family [[GH15]] glucoamylase from ''Rhizopus oryzae'' <cite>Liu2007</cite>. The first CBM21 complex structures were determined by X-ray crystallography for that domain binding to β -cyclodextrin or maltoheptaose <cite>Tung2008</cite>.<br />
<br />
== Novel Applications ==<br />
The CBM21 from ''Rhizopus oryzae'' glucoamylase has been introduced as a novel affinity purification tag <cite>Lin2009</cite>. <br />
<br />
== References ==<br />
<biblio><br />
#Chou2006 pmid=16509822<br />
#Chu2014 pmid=24108499<br />
#Liu2007 pmid=17117925<br />
#Tung2008 pmid=18588504<br />
#Jiang2012 pmid=22815939<br />
#Stephen2012 pmid=23226294<br />
#Ashikari1986 Ashikari T, Nakamura N, Tanaka Y, Kiuchi N, Shibano Y, Tanaka T, Amachi T, and Yoshizumi H. “Rhizopus raw-starch-degrading glucoamylase: its cloning and expression in yeast.” Agric. Biol. Chem. 1986; 50: 957-64.<br />
#Bui1996 pmid=8920185<br />
#Houghton-Larsen2003 pmid=12883866<br />
#Steyn1995 pmid=8529895<br />
#Kang2004 pmid=15043869<br />
#Møller2012 pmid=22949184<br />
#Chen2012 pmid=23166747<br />
#Machovic2005 pmid=16262690<br />
#Bork1998 pmid=9500672<br />
#Takahashi1982 pmid=6818228<br />
#Tanaka1986 Tanaka Y, Ashikari T, Nakamura N, Kiuchi N, Shibano Y, Amachi T, and Yoshizumi H. Comparison of amino acid sequences of three glucoamylases and their structure-function relationships. Agric. Biol. Chem. 1986; 50: 965-9.<br />
#Svensson1989 pmid=2481445<br />
#Machovic2006 pmid=17013558<br />
#Christiansen2009 pmid=19682075<br />
#Lin2009 pmid=19297701 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM021]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10675Carbohydrate Binding Module Family 482015-07-07T12:32:14Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 Koay2010 Meekins2014 Polekhina2005 Katsuya1998 Feese2000 Abad2002 Timmis2005 Leiros2006 Mikami2006 Amodeo2007 Woo2008 Gourlay2009 Turkenburg2009 Pal2010 Song2010 Vander-Kooi2010 Vester-Christensen2010 Noguchi2011 Moeller2012 Okazaki2012 Park2013 Xiao2013 Calabrese2014 Sim2014 Xu2014 Li2015 Moeller2015a Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family [[GH13]] precedes the catalytic TIM-barrel. This is the case of isoamylase <cite>Katsuya1998 Sim2014</cite>, maltooligosyltrehalohydrolase <cite>Feese2000 Timmis2005 Leiros2006</cite>, branching enzyme <cite>Chaen2012 Abad2002 Pal2010 Noguchi2011 Palomo2009</cite>, debranching enzyme <cite>Woo2008 Song2010</cite>, pullulanase <cite>Mikami2006 Gourlay2009 Turkenburg2009 Xu2014</cite>, limit dextrinase <cite>Vester-Christensen2010 Moeller2012 Moeller2015a Moeller2015b</cite> and a bifunctional α-amylase/cyclomaltodextrinase <cite>Park2013</cite>. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain <cite>Meekins2014 Vander-Kooi2010 Gentry2009</cite>. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule <cite>Koay2010 Polekhina2005 Mobbs2015 Xiao2013 Calabrese2014 Li2015</cite>; the same applies for AMPK’s yeast homologue SNF1 <cite>Amodeo2007</cite>. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis <cite>Peng2014a</cite>. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family CBM48 are most closely related to those from the family [[CBM20]] <cite>Janecek2011</cite> and, in a wider sense, also to those from families [[CBM21]], [[CBM53]] <cite>Machovic2006a Christiansen2009</cite> and the recently established family [[CBM69]] <cite>Peng2014b</cite>.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa <cite>Machovic2006a</cite> and then defined within the CAZy database as an independent CBM family <cite>Machovic2008 Cantarel2009</cite>.<br />
;First Structural Characterization<br />
Based on current knowledge <cite>Janecek2011 Machovic2008 Cantarel2009</cite>, the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa <cite>Katsuya1998</cite>. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK <cite>Polekhina2005</cite>, but it is of note that at that time the family CBM48 was not established <cite>Machovic2006b</cite>. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander-Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10674Carbohydrate Binding Module Family 482015-07-07T12:29:12Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 Koay2010 Meekins2014 Polekhina2005 Katsuya1998 Feese2000 Abad2002 Timmis2005 Leiros2006 Mikami2006 Amodeo2007 Woo2008 Gourlay2009 Turkenburg2009 Pal2010 Song2010 Vander-Kooi2010 Vester-Christensen2010 Noguchi2011 Moeller2012 Okazaki2012 Park2013 Xiao2013 Calabrese2014 Sim2014 Xu2014 Li2015 Moeller2015a Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family [[GH13]] precedes the catalytic TIM-barrel. This is the case of isoamylase <cite>Katsuya1998 Sim2014</cite>, maltooligosyltrehalohydrolase <cite>Feese2000 Timmis2005 Leiros2006</cite>, branching enzyme <cite>Chaen2012 Abad2002 Pal2010 Noguchi2011 Palomo2009</cite>, debranching enzyme <cite>Woo2008 Song2010</cite>, pullulanase <cite>Mikami2006 Gourlay2009 Turkenburg2009 Xu2014</cite>, limit dextrinase <cite>Vester-Christensen2010 Moeller2012 Moeller2015a Moeller2015b</cite> and a bifunctional α-amylase/cyclomaltodextrinase <cite>Park2013</cite>. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain <cite>Meekins2014 Vander-Kooi2010 Gentry2009</cite>. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule <cite>Koay2010 Polekhina2005 Mobbs2015 Xiao2013 Calabrese2014 Li2015</cite>; the same applies for AMPK’s yeast homologue SNF1 <cite>Amodeo2007</cite>. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis <cite>Peng2014a</cite>. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family CBM48 are most closely related to those from the family [[CBM20]] <cite>Janecek2011</cite> and, in a wider sense, also to those from families [[CBM21]], [[CBM53]] <cite>Machovic2006a Christiansen2009</cite> and the recently established family [[CBM69]] <cite>Peng2014b</cite>.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander-Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10673Carbohydrate Binding Module Family 482015-07-07T12:28:20Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 Koay2010 Meekins2014 Polekhina2005 Katsuya1998 Feese2000 Abad2002 Timmis2005 Leiros2006 Mikami2006 Amodeo2007 Woo2008 Gourlay2009 Turkenburg2009 Pal2010 Song2010 Vander-Kooi2010 Vester-Christensen2010 Noguchi2011 Moeller2012 Okazaki2012 Park2013 Xiao2013 Calabrese2014 Sim2014 Xu2014 Li2015 Moeller2015a Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family [[GH13]] precedes the catalytic TIM-barrel. This is the case of isoamylase <cite>Katsuya1998 Sim2014</cite>, maltooligosyltrehalohydrolase <cite>Feese2000 Timmis2005 Leiros2006</cite>, branching enzyme <cite>Chaen2012 Abad2002 Pal2010 Noguchi2011 Palomo2009</cite>, debranching enzyme <cite>Woo2008 Song2010</cite>, pullulanase <cite>Mikami2006 Gourlay2009 Turkenburg2009 Xu2014</cite>, limit dextrinase <cite>Vester-Christensen2010 Moeller2012 Moeller2015a Moeller2015b</cite> and a bifunctional α-amylase/cyclomaltodextrinase <cite>Park2013</cite>. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain <cite>Meekins2014 Vander-Kooi2010 Gentry2009</cite>. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule <cite>Koay2015 Polekhina2005 Mobbs2015 Xiao2013 Calabrese2014 Li2015</cite>; the same applies for AMPK’s yeast homologue SNF1 <cite>Amodeo2007</cite>. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis <cite>Peng2014a</cite>. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family CBM48 are most closely related to those from the family [[CBM20]] <cite>Janecek2011</cite> and, in a wider sense, also to those from families [[CBM21]], [[CBM53]] <cite>Machovic2006a Christiansen2009</cite> and the recently established family [[CBM69]] <cite>Peng2014b</cite>.<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander-Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10672Carbohydrate Binding Module Family 482015-07-07T12:12:34Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 Koay2010 Meekins2014 Polekhina2005 Katsuya1998 Feese2000 Abad2002 Timmis2005 Leiros2006 Mikami2006 Amodeo2007 Woo2008 Gourlay2009 Turkenburg2009 Pal2010 Song2010 Vander-Kooi2010 Vester-Christensen2010 Noguchi2011 Moeller2012 Okazaki2012 Park2013 Xiao2013 Calabrese2014 Sim2014 Xu2014 Li2015 Moeller2015a Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander-Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10671Carbohydrate Binding Module Family 482015-07-07T12:11:36Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 Koay2010 Meekins2014 Polekhina2005 Katsuya1998 Feese2000 Abad2002 Timmis2005 Leiros2006 Mikami2006 Amodeo2007 Woo2008 Gourlay2009 Turkenburg2009 Pal2010 Song2010 VanderKooi2010 Vester-Christensen2010 Noguchi2011 Moeller2012 Okazaki2012 Park2013 Xiao2013 Calabrese2014 Sim2014 Xu2014 Li2015 Moeller2015a Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10670Carbohydrate Binding Module Family 482015-07-07T12:10:41Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 Koay2010 Meekins2014 Polekhina2005 Katsuya1998 Feese2000 Abad2002 Timmis2005 Leiros2006 Mikami2006 Amodeo2007 Woo2008 Gourlay2009 Turkenburg2009 Pal2010 Song2010 Vander Kooi2010 Vester-Christensen2010 Noguchi2011 Moeller2012 Okazaki2012 Park2013 Xiao2013 Calabrese2014 Sim2014 Xu2014 Li2015 Moeller2015a Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10669Carbohydrate Binding Module Family 482015-07-07T12:06:07Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012 - Polekhina2005,Katsuya1998 - Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10668Carbohydrate Binding Module Family 482015-07-07T12:04:50Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012-Polekhina2005,Katsuya1998-Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[CBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10667Carbohydrate Binding Module Family 482015-07-07T12:04:03Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography <cite>Chaen2012-Polekhina2005,Katsuya1998-Moeller2015b</cite>, but also by NMR <cite>Mobbs2015</cite>. The structure is a typical β-sandwich with one well-defined binding site <cite>Polekhina2005</cite>. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) <cite>Polekhina2005</cite>, the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK <cite>Koay2010 Polekhina2005 Mobbs2015</cite>, and family [[GH13]] branching enzyme <cite>Chaen2012</cite> and starch excess4 (SEX4) protein <cite>Meekins2014</cite> both from plants. Notably, in complexes of the rice starch branching enzyme <cite>Chaen2012</cite> and the SEX4 protein <cite>Meekins2014</cite> with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related [[GBM20]] and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family [[GH13]] <cite>Janecek2011</cite>, but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands <cite>Chaen2012</cite>.<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10666Carbohydrate Binding Module Family 482015-07-07T11:57:57Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>Mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography [1-4,6-30], but also by NMR [5]. The structure is a typical β-sandwich with one well-defined binding site [4]. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) [4], the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK [2,4,5], and family GH13 branching enzyme [1] and starch excess4 (SEX4) protein [3] both from plants. Notably, in complexes of the rice starch branching enzyme [1] and the SEX4 protein [3] with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related CBM20 and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family GH13 [31], but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands [1].<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10665Carbohydrate Binding Module Family 482015-07-07T11:57:02Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose <cite>Chaen2012</cite>, maltooligosaccharides <cite>Koay2010</cite>, maltoheptaose <cite>Meekins2014</cite>, β-cyclodextrin <cite>Polekhina2005</cite>, single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose <cite>Koay2010</cite> and single α-1,6-branched glucosyl β-cyclodextrin <cite>mobbs2015</cite>. <br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography [1-4,6-30], but also by NMR [5]. The structure is a typical β-sandwich with one well-defined binding site [4]. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) [4], the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK [2,4,5], and family GH13 branching enzyme [1] and starch excess4 (SEX4) protein [3] both from plants. Notably, in complexes of the rice starch branching enzyme [1] and the SEX4 protein [3] with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related CBM20 and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family GH13 [31], but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands [1].<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
#Chaen2012 pmid=22771800<br />
#Koay2010 pmid=20637197<br />
#Meekins2014 pmid=24799671<br />
#Polekhina2005 pmid=16216577<br />
#Mobbs2015 pmid=25774984<br />
#Katsuya1998 pmid=9719642<br />
#Feese2000 pmid=10926520<br />
#Abad2002 pmid=12196524<br />
#Timmis2005 pmid=15784255<br />
#Leiros2006 pmid=16421442<br />
#Mikami2006 pmid=16650854<br />
#Amodeo2007 pmid=17851534<br />
#Woo2008 pmid=18703518<br />
#Gourlay2009 pmid=19329633<br />
#Turkenburg2009 pmid=19382205<br />
#Pal2010 pmid=20444687<br />
#Song2010 pmid=20187119<br />
#Vander Kooi2010 pmid=20679247<br />
#Vester-Christensen2010 pmid=20863834<br />
#Noguchi2011 pmid=21493662<br />
#Moeller2012 pmid=22949184<br />
#Okazaki2012 pmid=22334583<br />
#Park2013 pmid=22902546<br />
#Xiao2013 pmid=24352254<br />
#Calabrese2014 pmid=25066137<br />
#Sim2014 pmid=24993830<br />
#Xu2014 pmid=24375572<br />
#Li2015 pmid=25412657<br />
#Moeller2015a pmid=25792743<br />
#Moeller2015b pmid=25562209<br />
#Janecek2011 pmid=22112614<br />
#Palomo2009 pmid=19139240<br />
#Gentry2009 pmid=19818631<br />
#Peng2014a pmid=24456533<br />
#Machovic2006a pmid=17084392<br />
#Christiansen2009 pmid=19682075<br />
#Peng2014b pmid=24613924<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
#Cantarel2009 pmid=18838391<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_21&diff=10664Carbohydrate Binding Module Family 212015-07-07T11:10:22Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
* [[Responsible Curator]]s: ^^^Birte Svensson^^^ and ^^^Stefan Janecek^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM21.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Modules from family CBM21 bind to the α-glucan starch and oligosaccharides derived from starch or related to such oligosaccharides that contain α-1,4-linked glucose and/or α-1,6-linked glucose including maltose through maltoheptaose, β- and γ-cyclodextrins, isomaltotriose and isomaltotetraose [1-4]. CBM21 also interacts with amylose and alters its ultrastructure as demonstrated by atomic force microscopy [5]. Circular permutation enhanced the affinity for amylose [6]. The domain has been described as providing mainly glucoamylase and α-amylase with the ability to bind onto raw-starch (starch granules) [7-11] .<br />
<br />
''Note: Here is an example of how to insert references in the text, together with the "biblio" section below:'' Please see these references for an essential introduction to the CAZy classification system: <cite>DaviesSinnott2008 Cantarel2009</cite>. CBMs, in particular, have been extensively reviewed <cite>Boraston2004 Hashimoto2006 Shoseyov2006 Guillen2010</cite>.<br />
<br />
== Structural Features ==<br />
Structures of CBM21 have been determined by NMR and X-ray crystallography both in free and in carbohydrate complexed form. They adopt a common b-sandwich fold and have two binding sites accommodating carbohydrate ligands similarly to other starch binding domains. The binding sites contain aromatic side chains participating in carbohydrate interaction. Initially it was described by modelling using an NMR structure of a CBM20 as template [1] and thereafter by docking onto the NMR structure determined for CBM21 from the family GH15 Rhizopus oryzae glucoamylase [3]. The crystal structure determined for this CBM21 in complex with b-cyclodextrin or maltoheptaose identified W47, Y83 and Y94 interacting at site I and Y32 and F58 at site II for both ligands [4]. Site I requires ligands with DP > 3 for binding [2]. A CBM21-like domain was identified in the crystal structure of barley family GH13 limit dextrinase [12] .<br />
<br />
== Functionalities == <br />
CBM21s are mainly associated with some fungal glucoamylases and α-amylases of the family GH15 [7-9] and GH13 [10,11], respectively. This was confirmed by an exhaustive evolutionary analysis of 85 fungal genomes [13]. In both cases, i.e. in GH15 glucoamylases and GH13 α-amylases, the CBM21 precedes the catalytic domain [14]. The CBM21 is present also as a part of the regulatory subunit of Ser/Thr-specific protein phosphatases that directs the protein phosphatase to glycogen [15]. Recently, a structural comparison identified an N-terminal CBM21-like domain in the barley GH13 limit dextrinase [7], where it is followed by the module from the family CBM48 succeeded by the catalytic TIM-barrel .<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
Family CBM21 was first observed as an N-terminally located domain in glucoamylase from Rhizopus oryzae [7]. The function was ascribed based on comparison of multiple forms of the glucoamylase [7,16] and amino acid sequence alignment [17]. The CBM21 sequence was revealed as related to that of the starch binding domain of Aspergillus niger glucoamylase [18], which has been assigned the family CBM20 [14,19,20] .<br />
;First Structural Characterization<br />
The first CBM21 three-dimensional structure was determined by NMR for the module from the family GH15 glucoamylase from Rhizopus oryzae [3]. The first CBM21 complex structures were determined by X-ray crystallography for that domain binding to b-cyclodextrin or maltoheptaose [4] .<br />
<br />
== Novel Applications ==<br />
The CBM21 from Rhizopus oryzae glucoamylase has been introduced as a novel affinity purification tag [21]. <br />
<br />
== References ==<br />
<biblio><br />
#Chou2006 pmid=16509822<br />
#Chu2014 pmid=24108499<br />
#Liu2007 pmid=17117925<br />
#Tung2008 pmid=18588504<br />
#Jiang2012 pmid=22815939<br />
#Stephen2012 pmid=23226294<br />
#Ashikari1986 Ashikari T, Nakamura N, Tanaka Y, Kiuchi N, Shibano Y, Tanaka T, Amachi T, and Yoshizumi H. “Rhizopus raw-starch-degrading glucoamylase: its cloning and expression in yeast.” Agric. Biol. Chem. 1986; 50: 957-64.<br />
#Bui1996 pmid=8920185<br />
#Houghton-Larsen pmid=12883866<br />
#Steyn1995 pmid=8529895<br />
#Kang2004 pmid=15043869<br />
#Møller2012 pmid=22949184<br />
#Chen2012 pmid=23166747<br />
#Machovic2005 pmid=16262690<br />
#Bork1998 pmid=9500672<br />
#Takahashi1982 pmid=6818228<br />
#Tanaka1986 Tanaka Y, Ashikari T, Nakamura N, Kiuchi N, Shibano Y, Amachi T, and Yoshizumi H. Comparison of amino acid sequences of three glucoamylases and their structure-function relationships. Agric. Biol. Chem. 1986; 50: 965-9.<br />
#Svensson1989 pmid=2481445<br />
#Machovic2006 pmid=17013558<br />
#Christiansen2009 pmid=19682075<br />
#Lin2009 pmid=19297701 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM021]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10663Carbohydrate Binding Module Family 482015-07-07T11:06:15Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose [1], maltooligosaccharides [2], maltoheptaose [3], β-cyclodextrin [4], single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose [2] and single α-1,6-branched glucosyl β-cyclodextrin [5]. <br />
''Note: Here is an example of how to insert references in the text, together with the "biblio" section below:'' Please see these references for an essential introduction to the CAZy classification system: <cite>DaviesSinnott2008 Cantarel2009</cite>. CBMs, in particular, have been extensively reviewed <cite>Boraston2004 Hashimoto2006 Shoseyov2006 Guillen2010</cite>.<br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography [1-4,6-30], but also by NMR [5]. The structure is a typical β-sandwich with one well-defined binding site [4]. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) [4], the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK [2,4,5], and family GH13 branching enzyme [1] and starch excess4 (SEX4) protein [3] both from plants. Notably, in complexes of the rice starch branching enzyme [1] and the SEX4 protein [3] with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related CBM20 and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family GH13 [31], but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands [1].<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37].<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
800x600<br />
<br />
#Chaen2012 pmid=22771800<br />
<br />
#Koay2010 pmid=20637197<br />
<br />
#Meekins2014 pmid=24799671<br />
<br />
#Polekhina2005 pmid=16216577<br />
<br />
#Mobbs2015 pmid=25774984<br />
<br />
#Katsuya1998 pmid=9719642<br />
<br />
#Feese2000 pmid=10926520<br />
<br />
#Abad2002 pmid=12196524<br />
<br />
#Timmis2005 pmid=15784255<br />
<br />
#Leiros2006 pmid=16421442<br />
<br />
#Mikami2006 pmid=16650854<br />
<br />
#Amodeo2007 pmid=17851534<br />
<br />
#Woo2008 pmid=18703518<br />
<br />
#Gourlay2009 pmid=19329633<br />
<br />
#Turkenburg2009 pmid=19382205<br />
<br />
#Pal2010 pmid=20444687<br />
<br />
#Song2010 pmid=20187119<br />
<br />
#Vander Kooi2010 pmid=20679247<br />
<br />
#Vester-Christensen2010 pmid=20863834<br />
<br />
#Noguchi2011 pmid=21493662<br />
<br />
#Moeller2012 pmid=22949184<br />
<br />
#Okazaki2012 pmid=22334583<br />
<br />
#Park2013 pmid=22902546<br />
<br />
#Xiao2013 pmid=24352254<br />
<br />
#Calabrese2014 pmid=25066137<br />
<br />
#Sim2014 pmid=24993830<br />
<br />
#Xu2014 pmid=24375572<br />
<br />
#Li2015 pmid=25412657<br />
<br />
#Moeller2015a pmid=25792743<br />
<br />
#Moeller2015b pmid=25562209<br />
<br />
#Janecek2011 pmid=22112614<br />
<br />
#Palomo2009 pmid=19139240<br />
<br />
#Gentry2009 pmid=19818631<br />
<br />
#Peng2014a pmid=24456533<br />
<br />
#Machovic2006a pmid=17084392<br />
<br />
#Christiansen2009 pmid=19682075<br />
<br />
#Peng2014b pmid=24613924<br />
<br />
#Machovic2008 Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. ([http://dx.doi.org/10.2478/s11756-008-0162-4 DOI: 10.2478/s11756-008-0162-4])<br />
<br />
#Cantarel2009 pmid=18838391<br />
<br />
#Machovic2006b pmid=17013558 <br />
</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecekhttps://www.cazypedia.org/index.php?title=Carbohydrate_Binding_Module_Family_48&diff=10662Carbohydrate Binding Module Family 482015-07-07T11:05:56Z<p>Stefan Janecek: </p>
<hr />
<div><!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption --><br />
{{UnderConstruction}}<br />
* [[Author]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
* [[Responsible Curator]]s: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^<br />
----<br />
<br />
<!-- The data in the table below should be updated by the Author/Curator according to current information on the family --><br />
<div style="float:right"><br />
{| {{Prettytable}} <br />
|-<br />
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br />
|-<br />
| colspan="2" |{{CAZyDBlink}}CBM48.html<br />
|}<br />
</div><br />
<!-- This is the end of the table --><br />
<br />
== Ligand specificities ==<br />
Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose [1], maltooligosaccharides [2], maltoheptaose [3], β-cyclodextrin [4], single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose [2] and single α-1,6-branched glucosyl β-cyclodextrin [5]. <br />
''Note: Here is an example of how to insert references in the text, together with the "biblio" section below:'' Please see these references for an essential introduction to the CAZy classification system: <cite>DaviesSinnott2008 Cantarel2009</cite>. CBMs, in particular, have been extensively reviewed <cite>Boraston2004 Hashimoto2006 Shoseyov2006 Guillen2010</cite>.<br />
<br />
== Structural Features ==<br />
There is a number of family CBM48 structures solved mostly by X-ray crystallography [1-4,6-30], but also by NMR [5]. The structure is a typical β-sandwich with one well-defined binding site [4]. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) [4], the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK [2,4,5], and family GH13 branching enzyme [1] and starch excess4 (SEX4) protein [3] both from plants. Notably, in complexes of the rice starch branching enzyme [1] and the SEX4 protein [3] with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related CBM20 and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family GH13 [31], but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands [1].<br />
<br />
== Functionalities == <br />
The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6,26], maltooligosyltrehalohydrolase [7,9,10], branching enzyme [1,8,16,20,32], debranching enzyme [13,17], pullulanase [11,14,15,27], limit dextrinase [19,21,29,30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3,18,33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2,4,5,24,25,28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 [37] .<br />
<br />
== Family Firsts ==<br />
;First Identified<br />
The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].<br />
;First Structural Characterization<br />
Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40]. <br />
<br />
== References ==<br />
<biblio><br />
800x600<br />
<br />
#Chaen2012 pmid=22771800<br />
<br />
#Koay2010 pmid=20637197<br />
<br />
#Meekins2014 pmid=24799671<br />
<br />
#Polekhina2005 pmid=16216577<br />
<br />
#Mobbs2015 pmid=25774984<br />
<br />
#Katsuya1998 pmid=9719642<br />
<br />
#Feese2000 pmid=10926520<br />
<br />
#Abad2002 pmid=12196524<br />
<br />
#Timmis2005 pmid=15784255<br />
<br />
#Leiros2006 pmid=16421442<br />
<br />
#Mikami2006 pmid=16650854<br />
<br />
#Amodeo2007 pmid=17851534<br />
<br />
#Woo2008 pmid=18703518<br />
<br />
#Gourlay2009 pmid=19329633<br />
<br />
#Turkenburg2009 pmid=19382205<br />
<br />
#Pal2010 pmid=20444687<br />
<br />
#Song2010 pmid=20187119<br />
<br />
#Vander Kooi2010 pmid=20679247<br />
<br />
#Vester-Christensen2010 pmid=20863834<br />
<br />
#Noguchi2011 pmid=21493662<br />
<br />
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</biblio><br />
<br />
[[Category:Carbohydrate Binding Module Families|CBM048]]</div>Stefan Janecek