Glycoside Hydrolase Family 128 - Revision history

Harry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

2021-12-18T21:14:47Z

Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

Harry Brumer: Fixed Curator Approved tag

2020-09-29T19:47:45Z

Fixed Curator Approved tag

Mario Murakami at 11:38, 29 September 2020

2020-09-29T11:38:47Z

Mario Murakami at 11:30, 29 September 2020

2020-09-29T11:30:45Z

Mario Murakami at 11:26, 29 September 2020

2020-09-29T11:26:38Z

Mario Murakami at 11:16, 29 September 2020

2020-09-29T11:16:17Z

Mario Murakami at 11:11, 29 September 2020

2020-09-29T11:11:08Z

Mario Murakami at 11:04, 29 September 2020

2020-09-29T11:04:54Z

Harry Brumer: Made "Clustering" section a subsection of Substrate Specificites and shortened it.

2020-08-17T15:37:13Z

Made "Clustering" section a subsection of Substrate Specificites and shortened it.

Harry Brumer: minor grammatical improvements

2020-08-17T15:25:51Z

minor grammatical improvements

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 {{CuratorApproved}}
-* [[Author]]: ^^^Yuichi Sakamoto^^^ and ^^^Camilla Santos^^^
+* [[Author]]: [[User:Yuichi Sakamoto|Yuichi Sakamoto]] and [[User:Camilla Santos|Camilla Santos]]
-* [[Responsible Curator]]:  ^^^Mario Murakami^^^
+* [[Responsible Curator]]:  [[User:Mario Murakami|Mario Murakami]]
 ----
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 === Clustering of GH128 ===
 [[Image:Santos_GH128_final.png|thumb|right|250px|Figure 1. Clustering of the GH128 family into seven subgroups. Adapted from <cite>Santos2020</cite>.]]
-GH128 was created based on the study of ^^^Yuichi Sakamoto^^^ and colleagues <cite>Sakamoto2011</cite>. Years later, a group headed by ^^^Mario Murakami^^^ explored the functional and structural diversity of this family <cite>Santos2020</cite>. For this purpose, they employed phylogenetic and Sequence Similarity Network (SSN, <cite>Atkinson2009</cite>) analyses to segregate the family into putative isofunctional subgroups. The SSN analysis resulted in two discrete clusters (subgroups VI and VII) and a third cluster that was further subdivided into five subgroups (I to V) based on SSN alignment scores and evolutionary closeness (Fig. 1). At least one member of each subgroup was biochemically and structurally characterized. Subgroups I and II were found to be predominantly present in bacteria, and the subgroups III to VII are mostly found in fungi. Bacterial enzymes are faster, feature a substrate-interacting "hydrophobic knuckle" (see [[#Three-dimensional structures]]) and attack the &beta;-1,3-glucan in an endo mode of action, which is compatible with their biological functions (nutrition and competition). Fungal &beta;-1,3-glucanases are known to act on remodeling of their own cell walls. Therefore, these enzymes are slower, more diverse in terms of strategies for substrate recognition (flattening mechanism – subgroups IV and VI; and hydrophobic knuckle – subgroups III, V and VII) and modes of action (exo-enzymes – subgroups III, V and VI; endo-enzymes – subgroup IV; and oligosaccharide binding proteins – subgroup VII).
+GH128 was created based on the study of [[User:Yuichi Sakamoto|Yuichi Sakamoto]] and colleagues <cite>Sakamoto2011</cite>. Years later, a group headed by [[User:Mario Murakami|Mario Murakami]] explored the functional and structural diversity of this family <cite>Santos2020</cite>. For this purpose, they employed phylogenetic and Sequence Similarity Network (SSN, <cite>Atkinson2009</cite>) analyses to segregate the family into putative isofunctional subgroups. The SSN analysis resulted in two discrete clusters (subgroups VI and VII) and a third cluster that was further subdivided into five subgroups (I to V) based on SSN alignment scores and evolutionary closeness (Fig. 1). At least one member of each subgroup was biochemically and structurally characterized. Subgroups I and II were found to be predominantly present in bacteria, and the subgroups III to VII are mostly found in fungi. Bacterial enzymes are faster, feature a substrate-interacting "hydrophobic knuckle" (see [[#Three-dimensional structures]]) and attack the &beta;-1,3-glucan in an endo mode of action, which is compatible with their biological functions (nutrition and competition). Fungal &beta;-1,3-glucanases are known to act on remodeling of their own cell walls. Therefore, these enzymes are slower, more diverse in terms of strategies for substrate recognition (flattening mechanism – subgroups IV and VI; and hydrophobic knuckle – subgroups III, V and VII) and modes of action (exo-enzymes – subgroups III, V and VI; endo-enzymes – subgroup IV; and oligosaccharide binding proteins – subgroup VII).
 == Kinetics and Mechanism ==

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 * [[Author]]: ^^^Yuichi Sakamoto^^^ and ^^^Camilla Santos^^^
 * [[Responsible Curator]]:  ^^^Mario Murakami^^^
 ----

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 == Family Firsts ==
-;First stereochemistry determination: predicted to be retaining by membership in Clan GH-A <cite>Sakamoto2011</cite> and further validated by <sup>1</sup>H-NMR of products of the ''A. mediterranei'' endo-&beta;-1,3-glucanase (AmGH128_I) <cite>Santos2020</cite>.
+;First stereochemistry determination: predicted to be retaining by membership in Clan GH-A <cite>Sakamoto2011</cite> and further validated by <sup>1</sup>H-NMR analysis of laminarin products generated by the ''A. mediterranei'' endo-&beta;-1,3-glucanase (AmGH128_I) <cite>Santos2020</cite>.
 ;First catalytic nucleophile identification: predicted by sequence alignment <cite>Sakamoto2011</cite> and confirmed by site-directed mutagenesis of ''A. mediterranei'' endo-&beta;-1,3-glucanase (AmGH128_I) <cite>Santos2020</cite>.
 ;First general acid/base residue identification: predicted by sequence alignment <cite>Sakamoto2011</cite> and confirmed by site-directed mutagenesis of ''A. mediterranei'' endo-&beta;-1,3-glucanase (AmGH128_I) <cite>Santos2020</cite>.

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 * [[Author]]: ^^^Yuichi Sakamoto^^^ and ^^^Camilla Santos^^^
 * [[Responsible Curator]]:  ^^^Mario Murakami^^^
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 A three-dimensional homology model of ''L. edodes'' GLU1 indicated similarity with several (&beta;/&alpha;)<sub>8</sub>-barrel (TIM-barrel) structures, including a [[GH39]] &beta;-xylosidase and a [[GH5]] &beta;-mannanase <cite>Sakamoto2011</cite>. The fold resembling an (&beta;/&alpha;)<sub>8</sub>-barrel was further confirmed with the crystal structure determination of 9 members of the family <cite>Santos2020</cite>. However, in all structures, the helix &alpha;2 and the strand &beta;3 are strictly absent <cite>Santos2020</cite>. Moreover, some enzymes such as the endo-&beta;-1,3-glucanase from ''L. edodes'' (GLU1) and the exo-&beta;-1,3-glucanase from ''C. neoformans'', also lack the helices &alpha;1 and &alpha;3, respectively <cite>Santos2020</cite>.
-Two distinct modes of substrate binding were observed in the GH128 family <cite>Santos2020</cite>. The most widespread mode, termed the "hydrophobic knuckle", involves a tryptophan residue that interacts with four glucoside moieties from –5 to –2 and is fully complementary to the typically curved conformation of &beta;-1,3-glucan chains. The other mode, only observed in fungal members belonging to subgroups IV and VI, requires substrate conformational changes to allow the binding to the catalytic interface. In these fungal subgroups, the hydrophobic knuckle is absent and two aromatic residues, positioned at the -5 and -4 subsites, create a linearized cleft, which requires a 180° torsion in the glycosidic bond between the glycosyl moieties –2 and –3 in the &beta;-1,3-glucan chain for binding. This mode of substrate recognition is referred to as the "flattening" mechanism, due to the unusual, but also stereochemically favorable, conformation adopted by the substrate. It is notable that this mode of substrate binding has not been observed in other CAZy families active on &beta;-1,3-glucans.
+Two distinct modes of substrate binding were observed in the GH128 family <cite>Santos2020</cite>. The most widespread mode, termed as "hydrophobic knuckle", involves a tryptophan residue that interacts with four glucoside moieties from –5 to –2 and is fully complementary to the typically curved conformation of &beta;-1,3-glucan chains. The other mode, only observed in fungal members belonging to subgroups IV and VI, requires substrate conformational changes to allow the binding to the catalytic interface. In these fungal subgroups, the hydrophobic knuckle is absent and two aromatic residues, positioned at the -5 and -4 subsites, create a linearized cleft, which requires a 180° torsion in the glycosidic bond between the glycosyl moieties –2 and –3 in the &beta;-1,3-glucan chain for binding. This mode of substrate recognition is referred to as the "flattening" mechanism, due to the unusual, but also stereochemically favorable, conformation adopted by the substrate. It is notable that this mode of substrate binding has not been observed in other CAZy families active on &beta;-1,3-glucans.
 == Family Firsts ==

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 A three-dimensional homology model of ''L. edodes'' GLU1 indicated similarity with several (&beta;/&alpha;)<sub>8</sub>-barrel (TIM-barrel) structures, including a [[GH39]] &beta;-xylosidase and a [[GH5]] &beta;-mannanase <cite>Sakamoto2011</cite>. The fold resembling an (&beta;/&alpha;)<sub>8</sub>-barrel was further confirmed with the crystal structure determination of 9 members of the family <cite>Santos2020</cite>. However, in all structures, the helix &alpha;2 and the strand &beta;3 are strictly absent <cite>Santos2020</cite>. Moreover, some enzymes such as the endo-&beta;-1,3-glucanase from ''L. edodes'' (GLU1) and the exo-&beta;-1,3-glucanase from ''C. neoformans'', also lack the helices &alpha;1 and &alpha;3, respectively <cite>Santos2020</cite>.
-Two distinct modes of substrate binding were observed in the GH128 family <cite>Santos2020</cite>. The most widespread mode, termed as "hydrophobic knuckle", involves a tryptophan residue that interacts with four glucoside moieties from –5 to –2 and is fully complementary to the typically curved conformation of &beta;-1,3-glucan chains. The other mode, only observed in fungal members belonging to subgroups IV and VI, requires substrate conformational changes to allow the binding to the catalytic interface. In these fungal subgroups, the hydrophobic knuckle is absent and two aromatic residues, positioned at the -5 and -4 subsites, create a linearized cleft, which requires a 180° torsion in the glycosidic bond between the glycosyl moieties –2 and –3 in the &beta;-1,3-glucan chain for binding. This mode of substrate recognition is referred to as the "flattening" mechanism, due to the unusual, but also stereochemically favorable, conformation adopted by the substrate. It is notable that this mode of substrate binding has not been observed in other CAZy families active on &beta;-1,3-glucans.
+Two distinct modes of substrate binding were observed in the GH128 family <cite>Santos2020</cite>. The most widespread mode, termed the "hydrophobic knuckle", involves a tryptophan residue that interacts with four glucoside moieties from –5 to –2 and is fully complementary to the typically curved conformation of &beta;-1,3-glucan chains. The other mode, only observed in fungal members belonging to subgroups IV and VI, requires substrate conformational changes to allow the binding to the catalytic interface. In these fungal subgroups, the hydrophobic knuckle is absent and two aromatic residues, positioned at the -5 and -4 subsites, create a linearized cleft, which requires a 180° torsion in the glycosidic bond between the glycosyl moieties –2 and –3 in the &beta;-1,3-glucan chain for binding. This mode of substrate recognition is referred to as the "flattening" mechanism, due to the unusual, but also stereochemically favorable, conformation adopted by the substrate. It is notable that this mode of substrate binding has not been observed in other CAZy families active on &beta;-1,3-glucans.
 == Family Firsts ==

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 == Substrate specificities ==
-The first GH128 enzyme, GLU1, was cloned from ''Lentinula edodes'' fruiting bodies (shiitake mushroom) <cite>Sakamoto2011</cite>. GLU1 cleaves &beta;-1,3 linkages in various &beta;-glucans such as endogenous ''L. edodes'' lentinan, laminarin from ''Laminaria digitata'', pachyman from ''Poria cocos'', and curdlan from ''Alcaligenes faecalis'', but does not degrade &beta;-1,3-linkages within &beta;-1,3-1,4-glucans such as barley glucan, indicating the enzyme is categorized into EC [{{EClink}}3.2.1.39 3.2.1.39] <cite>Sakamoto2011</cite>. Further work with several GH128 members corroborated that this family is specific for &beta;-1,3-glucans <cite>Santos2020</cite>. In addition, it was demonstrated that bacterial members, such as those from ''Amycolatopsis mediterranei'' (subgroup I)  and ''Pseudomonas viridiflava'' (subgroup II), are endo-&beta;-1,3-glucanases that degrade these carbohydrates at higher rates <cite>Santos2020</cite>. Fungal GH128 members are more diverse in terms of activity: endo-&beta;-1,3-glucanases, represented by the GLU1 from ''L. edodes'' (subgroup IV) <cite>Sakamoto2011 Santos2020</cite>; exo-&beta;-1,3-glucanases that release trisaccharides (''Aureobsidium namibiae'') (subgroup VI) <cite>Santos2020</cite> and monosaccharides (''Cryptococcus neoformans'')  (subgroup V) from the reducing ends; and exo-&beta;-1,3-glucanases that release trisaccharides from the non-reducing ends of triple-helical &beta;-1,3-glucans, represented by the enzyme from ''Blastomyces gilchristii''  (subgroup III) <cite>Santos2020</cite>. Some fungal members from this family, such as those from ''Trichoderma gamsii'' and ''C. neoformans'', are devoid of catalytic activity but conserve the capacity to bind short &beta;-1,3-glucooligosaccharides (subgroup VII) <cite>Santos2020</cite>.
+The first GH128 enzyme, GLU1, was cloned from ''Lentinula edodes'' fruiting bodies (shiitake mushroom) <cite>Sakamoto2011</cite>. GLU1 cleaves &beta;-1,3 linkages in various &beta;-glucans such as endogenous ''L. edodes'' lentinan, laminarin from ''Laminaria digitata'', pachyman from ''Poria cocos'', and curdlan from ''Alcaligenes faecalis'', but does not degrade &beta;-1,3-linkages within &beta;-1,3-1,4-glucans such as barley glucan, indicating the enzyme is categorized into EC [{{EClink}}3.2.1.39 3.2.1.39] <cite>Sakamoto2011</cite>. Further work with several GH128 members corroborated that this family is specific for &beta;-1,3-glucans <cite>Santos2020</cite>. Bacterial members from ''Amycolatopsis mediterranei'' (subgroup I)  and ''Pseudomonas viridiflava'' (subgroup II)exhibit endo-&beta;-1,3-glucanase activity and catalytic rates notably higher than those observed for fungal members <cite>Santos2020</cite>. On the other hand, fungal members display diverse modes of action and substrate specificity. The GH128 members from ''Aureobsidium namibiae'' (subgroup VI) and ''Cryptococcus neoformans'' (subgroup V) are exo-&beta;-1,3-glucanases and release trisaccharides and monosaccharides from the reducing ends, respectively. The enzyme from ''Blastomyces gilchristii'' (subgroup III) is also an exo-&beta;-1,3-glucanase; however, it releases trisaccharides from the non-reducing ends of triple-helical &beta;-1,3-glucans. The founder member of the family, GLU1 from ''L. edodes'' (subgroup IV) is an endo-&beta;-1,3-glucanase with an atypical mode of substrate recognition as in the subgroup VI. Intriguingly, some fungal members from this family, such as those from ''Trichoderma gamsii'' and ''C. neoformans'', are devoid of catalytic activity but conserve the capacity to bind short &beta;-1,3-glucooligosaccharides (subgroup VII) <cite>Santos2020</cite>.
 === Clustering of GH128 ===

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 == Substrate specificities ==
-The first GH128 enzyme, GLU1, was cloned from ''Lentinula edodes'' fruiting bodies (shiitake mushroom) <cite>Sakamoto2011</cite>. GLU1 cleaves &beta;-1,3 linkages in various &beta;-glucans such as endogenous 'L. edodes'' lentinan, laminarin from ''Laminaria digitata'', pachyman from ''Poria cocos'', and curdlan from ''Alcaligenes faecalis'', but does not degrade &beta;-1,3-linkages within &beta;-1,3-1,4-glucans such as barley glucan, indicating the enzyme is categorized into EC [{{EClink}}3.2.1.39 3.2.1.39] <cite>Sakamoto2011</cite>. Further work with several GH128 members corroborated that this family is specific for &beta;-1,3-glucans <cite>Santos2020</cite>. In addition, it was demonstrated that bacterial members, such as those from ''Amycolatopsis mediterranei'' (subgroup I)  and ''Pseudomonas viridiflava'' (subgroup II), are endo-&beta;-1,3-glucanases that degrade these carbohydrates at higher rates <cite>Santos2020</cite>. Fungal GH128 members are more diverse in terms of activity: endo-&beta;-1,3-glucanases, represented by the GLU1 from ''L. edodes'' (subgroup IV) <cite>Sakamoto2011 Santos2020</cite>; exo-&beta;-1,3-glucanases that release trisaccharides (''Aureobsidium namibiae'') (subgroup VI) <cite>Santos2020</cite> and monosaccharides (''Cryptococcus neoformans'')  (subgroup V) from the reducing ends; and exo-&beta;-1,3-glucanases that release trisaccharides from the non-reducing ends of triple-helical &beta;-1,3-glucans, represented by the enzyme from ''Blastomyces gilchristii''  (subgroup III) <cite>Santos2020</cite>. Some fungal members from this family, such as those from ''Trichoderma gamsii'' and ''C. neoformans'', are devoid of catalytic activity but conserve the capacity to bind short &beta;-1,3-glucooligosaccharides (subgroup VII) <cite>Santos2020</cite>.
+The first GH128 enzyme, GLU1, was cloned from ''Lentinula edodes'' fruiting bodies (shiitake mushroom) <cite>Sakamoto2011</cite>. GLU1 cleaves &beta;-1,3 linkages in various &beta;-glucans such as endogenous ''L. edodes'' lentinan, laminarin from ''Laminaria digitata'', pachyman from ''Poria cocos'', and curdlan from ''Alcaligenes faecalis'', but does not degrade &beta;-1,3-linkages within &beta;-1,3-1,4-glucans such as barley glucan, indicating the enzyme is categorized into EC [{{EClink}}3.2.1.39 3.2.1.39] <cite>Sakamoto2011</cite>. Further work with several GH128 members corroborated that this family is specific for &beta;-1,3-glucans <cite>Santos2020</cite>. In addition, it was demonstrated that bacterial members, such as those from ''Amycolatopsis mediterranei'' (subgroup I)  and ''Pseudomonas viridiflava'' (subgroup II), are endo-&beta;-1,3-glucanases that degrade these carbohydrates at higher rates <cite>Santos2020</cite>. Fungal GH128 members are more diverse in terms of activity: endo-&beta;-1,3-glucanases, represented by the GLU1 from ''L. edodes'' (subgroup IV) <cite>Sakamoto2011 Santos2020</cite>; exo-&beta;-1,3-glucanases that release trisaccharides (''Aureobsidium namibiae'') (subgroup VI) <cite>Santos2020</cite> and monosaccharides (''Cryptococcus neoformans'')  (subgroup V) from the reducing ends; and exo-&beta;-1,3-glucanases that release trisaccharides from the non-reducing ends of triple-helical &beta;-1,3-glucans, represented by the enzyme from ''Blastomyces gilchristii''  (subgroup III) <cite>Santos2020</cite>. Some fungal members from this family, such as those from ''Trichoderma gamsii'' and ''C. neoformans'', are devoid of catalytic activity but conserve the capacity to bind short &beta;-1,3-glucooligosaccharides (subgroup VII) <cite>Santos2020</cite>.
 == Kinetics and Mechanism ==
@@ Line 41: / Line 45: @@
 Two distinct modes of substrate binding were observed in the GH128 family <cite>Santos2020</cite>. The most widespread mode, termed the "hydrophobic knuckle", involves a tryptophan residue that interacts with four glucoside moieties from –5 to –2 and is fully complementary to the typically curved conformation of &beta;-1,3-glucan chains. The other mode, only observed in fungal members belonging to subgroups IV and VI, requires substrate conformational changes to allow the binding to the catalytic interface. In these fungal subgroups, the hydrophobic knuckle is absent and two aromatic residues, positioned at the -5 and -4 subsites, create a linearized cleft, which requires a 180° torsion in the glycosidic bond between the glycosyl moieties –2 and –3 in the &beta;-1,3-glucan chain for binding. This mode of substrate recognition is referred to as the "flattening" mechanism, due to the unusual, but also stereochemically favorable, conformation adopted by the substrate. It is notable that the mode of substrate binding has not been observed in other CAZy families active on &beta;-1,3-glucans.
 == Family Firsts ==
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 #Sakamoto2011 pmid=21965406
 #Santos2020 pmid=32451508
-#Viborg2019 pmid=31501245
+#Atkinson2009 pmid=19190775
 </biblio>