Glycoside Hydrolase Family 5 - Revision history

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

2021-12-18T21:20:50Z

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

Mohamed Attia at 23:46, 21 March 2018

2018-03-21T23:46:46Z

Mohamed Attia at 22:13, 20 March 2018

2018-03-20T22:13:52Z

Mohamed Attia at 22:12, 20 March 2018

2018-03-20T22:12:17Z

Mohamed Attia at 23:02, 16 March 2018

2018-03-16T23:02:49Z

Mohamed Attia at 23:01, 16 March 2018

2018-03-16T23:01:11Z

Harry Brumer: Corrected Henrissat et al PNAS reference

2018-03-14T00:18:48Z

Corrected Henrissat et al PNAS reference

Harry Brumer at 00:16, 14 March 2018

2018-03-14T00:16:51Z

Mohamed Attia at 23:03, 13 March 2018

2018-03-13T23:03:00Z

Harry Brumer at 01:35, 27 February 2018

2018-02-27T01:35:30Z

@@ Line 1: / Line 1: @@
 <!-- CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Gideon Davies^^^ and ^^^Mohamed Attia^^^
+* [[Author]]: [[User:Gideon Davies|Gideon Davies]] and [[User:Mohamed Attia|Mohamed Attia]]
-* [[Responsible Curator]]:  ^^^Gideon Davies^^^
+* [[Responsible Curator]]:  [[User:Gideon Davies|Gideon Davies]]
 ----

@@ Line 44: / Line 44: @@
 By analogy with family [[GH26]] mannnanases <cite>Ducros</cite> and family [[GH2]] &beta;-mannosidases <cite>Tailford</cite> it would seem likely that GH5 mannanases use a different conformational itinerary to their glucosidase relatives, likely via a <sup>1</sup>''S''<sub>5</sub>-<sup>O</sup>''S''<sub>2</sub> glycosylation pathway and thus ''via'' a ''B''<sub>2,5</sub> (near) transition-state although direct evidence in this family is limited <cite>Vincent</cite>.  An interesting dissection of mannan-degrading enzyme systems has been provided by work in the Gilbert group on the diverse GH5 and [[GH26]] mannanases in ''Cellvibrio japonicus''(see for example <cite>Hogg,Tailford-2 Cartmell2008</cite>).
-The strict GH5_4 endo-xyloglucanases possess a wide active-site cleft that uniquely recognize the xylosyl substitutions of the polymeric substrate via discrete aromatic and hydrogen bond interactions. This is indeed contrary to the strict GH5 endo-glucanases which display a tight constriction in their active-site clefts leading to the apparent incapability of accommodating the highly branched xyloglucan substrate <cite>Naas2015</cite>. Notably, most of the GH5_4 endo-xyloglucanases cleave at the unbranched glucosyl units of the backbone due to the displayed constricted subsite -1 adjacent to the catalytic residues. Widening of that subsite, as observed in one of bovine rumen GH5_4 endoxyloglucanase, can clearly confer the ability to cleave at the substituted ''X'' unit leading to a different cleavage pattern <cite>dossantos2015</cite>. Although GH5_4 endo-xyloglucanases share amino acid identity as low as 30%, they display high substrate specificity towards xyloglucan which can be ultimately attributed to the high conservation of the amino acid residues interacting with the xyloglucan substrate in the active site cleft <cite>Attia2018</cite>.
+The strict GH5_4 endo-xyloglucanases possess a wide active-site cleft that uniquely recognize the xylosyl substitutions of the polymeric substrate via discrete aromatic and hydrogen bond interactions. This is indeed contrary to the strict GH5 endo-glucanases which display a tight constriction in their active-site clefts leading to the apparent incapability of accommodating the highly branched xyloglucan substrate <cite>Naas2015</cite>. Notably, most of the GH5_4 endo-xyloglucanases cleave at the unbranched glucosyl units of the backbone due to the displayed constricted subsite -1 adjacent to the catalytic residues. Widening of that subsite, as observed in one of bovine rumen GH5_4 endo-xyloglucanase, can clearly confer the ability to cleave at the substituted ''X'' unit leading to a different cleavage pattern <cite>dossantos2015</cite>. Although GH5_4 endo-xyloglucanases share amino acid identity as low as 30%, they display high substrate specificity towards xyloglucan which can be ultimately attributed to the high conservation of the amino acid residues interacting with the xyloglucan substrate in the active site cleft <cite>Attia2018</cite>.
 The GH5_34 enzymes target arabinoxylan through essential interactions with single arabinose substituents linked O3 to the xylose positioned in the active site -1 subsite <cite>Correia2011,Labourel2016</cite>. Very limited interactions with the xylan backbone is observed out with the -1 active site of the GH5_34 enzymes <cite>Labourel2016</cite>. This explains why these glycoside hydrolases cleave highly decorated glucuronoarabinoxylans that are recalcitrant to cleavage by classical xylanases found in GH10 and GH11.

@@ Line 1: / Line 1: @@
 <!-- CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Gideon Davies^^^
+* [[Author]]: ^^^Gideon Davies^^^ and ^^^Mohamed Attia^^^
 * [[Responsible Curator]]:  ^^^Gideon Davies^^^
 ----

@@ Line 44: / Line 44: @@
 By analogy with family [[GH26]] mannnanases <cite>Ducros</cite> and family [[GH2]] &beta;-mannosidases <cite>Tailford</cite> it would seem likely that GH5 mannanases use a different conformational itinerary to their glucosidase relatives, likely via a <sup>1</sup>''S''<sub>5</sub>-<sup>O</sup>''S''<sub>2</sub> glycosylation pathway and thus ''via'' a ''B''<sub>2,5</sub> (near) transition-state although direct evidence in this family is limited <cite>Vincent</cite>.  An interesting dissection of mannan-degrading enzyme systems has been provided by work in the Gilbert group on the diverse GH5 and [[GH26]] mannanases in ''Cellvibrio japonicus''(see for example <cite>Hogg,Tailford-2 Cartmell2008</cite>).
-The strict GH5_4 endo-xyloglucanases possess a wide active-site cleft that uniquely recognize the xylosyl substitutions of the polymeric substrate via discrete aromatic and hydrogen bond interactions. This is indeed contrary to the strict GH5 endo-glucanases which display a tight constriction in their active-site clefts leading to the apparent incapability of accommodating the highly branched xyloglucan substrate <cite>Naas2015</cite>. Notably, most of the GH5_4 endo-xyloglucanases cleave at the unbranched glucosyl units of the backbone due to the displayed constricted subsite -1 adjacent to the catalytic residues. Widening of that subsite, as observed in one of bovine rumen Gh5_4 endoxyloglucanase, can definitely confer the capability of cleavage at the substituted ''X'' unit leading to a different cleavage pattern <cite>dossantos2015</cite>.
+The strict GH5_4 endo-xyloglucanases possess a wide active-site cleft that uniquely recognize the xylosyl substitutions of the polymeric substrate via discrete aromatic and hydrogen bond interactions. This is indeed contrary to the strict GH5 endo-glucanases which display a tight constriction in their active-site clefts leading to the apparent incapability of accommodating the highly branched xyloglucan substrate <cite>Naas2015</cite>. Notably, most of the GH5_4 endo-xyloglucanases cleave at the unbranched glucosyl units of the backbone due to the displayed constricted subsite -1 adjacent to the catalytic residues. Widening of that subsite, as observed in one of bovine rumen GH5_4 endoxyloglucanase, can clearly confer the ability to cleave at the substituted ''X'' unit leading to a different cleavage pattern <cite>dossantos2015</cite>. Although GH5_4 endo-xyloglucanases share amino acid identity as low as 30%, they display high substrate specificity towards xyloglucan which can be ultimately attributed to the high conservation of the amino acid residues interacting with the xyloglucan substrate in the active site cleft <cite>Attia2018</cite>.
 The GH5_34 enzymes target arabinoxylan through essential interactions with single arabinose substituents linked O3 to the xylose positioned in the active site -1 subsite <cite>Correia2011,Labourel2016</cite>. Very limited interactions with the xylan backbone is observed out with the -1 active site of the GH5_34 enzymes <cite>Labourel2016</cite>. This explains why these glycoside hydrolases cleave highly decorated glucuronoarabinoxylans that are recalcitrant to cleavage by classical xylanases found in GH10 and GH11.

@@ Line 44: / Line 44: @@
 By analogy with family [[GH26]] mannnanases <cite>Ducros</cite> and family [[GH2]] &beta;-mannosidases <cite>Tailford</cite> it would seem likely that GH5 mannanases use a different conformational itinerary to their glucosidase relatives, likely via a <sup>1</sup>''S''<sub>5</sub>-<sup>O</sup>''S''<sub>2</sub> glycosylation pathway and thus ''via'' a ''B''<sub>2,5</sub> (near) transition-state although direct evidence in this family is limited <cite>Vincent</cite>.  An interesting dissection of mannan-degrading enzyme systems has been provided by work in the Gilbert group on the diverse GH5 and [[GH26]] mannanases in ''Cellvibrio japonicus''(see for example <cite>Hogg,Tailford-2 Cartmell2008</cite>).
-The strict GH5_4 endo-xyloglucanases possess a wide active-site cleft that uniquely recognize the xylosyl substitutions of the polymeric substrate via discrete aromatic and hydrogen bond interactions. This is indeed contrary to the strict GH5 endo-glucanases which display a tight constriction in their active-site clefts leading to the apparent incapability of accommodating the highly branched xyloglucan substrate <cite>Naas2015</cite>. Notably, most of the GH5_4 endo-xyloglucanases cleave at the unbranched glucosyl units of the backbone due to the displayed constricted subsite -1 adjacent to the catalytic residues. Widening of that subsite, as observed in one of bovine rumen Gh5_4 endoxyloglucanase, can definitely confer the capability of cleavage at the substituted ''X'' unit leading to a different cleavage pattern <cite>dos santos2015</cite>.
+The strict GH5_4 endo-xyloglucanases possess a wide active-site cleft that uniquely recognize the xylosyl substitutions of the polymeric substrate via discrete aromatic and hydrogen bond interactions. This is indeed contrary to the strict GH5 endo-glucanases which display a tight constriction in their active-site clefts leading to the apparent incapability of accommodating the highly branched xyloglucan substrate <cite>Naas2015</cite>. Notably, most of the GH5_4 endo-xyloglucanases cleave at the unbranched glucosyl units of the backbone due to the displayed constricted subsite -1 adjacent to the catalytic residues. Widening of that subsite, as observed in one of bovine rumen Gh5_4 endoxyloglucanase, can definitely confer the capability of cleavage at the substituted ''X'' unit leading to a different cleavage pattern <cite>dossantos2015</cite>.
 The GH5_34 enzymes target arabinoxylan through essential interactions with single arabinose substituents linked O3 to the xylose positioned in the active site -1 subsite <cite>Correia2011,Labourel2016</cite>. Very limited interactions with the xylan backbone is observed out with the -1 active site of the GH5_34 enzymes <cite>Labourel2016</cite>. This explains why these glycoside hydrolases cleave highly decorated glucuronoarabinoxylans that are recalcitrant to cleavage by classical xylanases found in GH10 and GH11.
@@ Line 61: / Line 61: @@
 <biblio>
 #Naas2015 pmid=26133573
-#dos santos2015 pmid=25714929
+#dossantos2015 pmid=25714929
 #Jenkins1995 pmid=7729513
 #Henrissat1995 pmid=7624375

@@ Line 29: / Line 29: @@
 == Substrate specificities ==
-GH5 is one of the largest of all CAZy [[glycoside hydrolase]] families. Previously known as "cellulase family A" <cite>Henrissat1989 Gilkes1991</cite>, a variety of specificities are now known in this family, notably endoglucanase (cellulase) and endomannanase, as well as exoglucanases, exomannanases and β-glucosidase and β-mannosidase. Other activities include 1,6-galactanase, 1,3-mannanase, 1,4-xylanase, endoglycoceramidase, as well as high specificity xyloglucanases. Family GH5 enzymes are found widely distributed across Archae, bacteria and eukaryotes, notably fungi and plants. There are no known human enzymes in GH5.  Following the reclassification of a number of GH5 members into [[GH30]] <cite>StJohn2010</cite>, a GH5 subfamily classification has been presented that delineates members into a number of monospecific and polyspecific clades <cite>Aspeborg2012</cite>. It should be noted that enzymes specifically targeting xylans are exclusively arabinoxylanases, and are found in subfamilies GH_21 <cite>Dodd2010</cite> and GH_34 <cite>Correia2011</cite>.
+GH5 is one of the largest of all CAZy [[glycoside hydrolase]] families. Previously known as "cellulase family A" <cite>Henrissat1989 Gilkes1991</cite>, a variety of specificities are now known in this family, notably endoglucanase (cellulase) and endomannanase, as well as exoglucanases, exomannanases and β-glucosidase and β-mannosidase. Other activities include 1,6-galactanase, 1,3-mannanase, 1,4-xylanase, endoglycoceramidase, as well as high specificity xyloglucanases. Family GH5 enzymes are found widely distributed across Archae, bacteria and eukaryotes, notably fungi and plants. There are no known human enzymes in GH5.  Following the reclassification of a number of GH5 members into [[GH30]] <cite>StJohn2010</cite>, a GH5 subfamily classification has been presented that delineates members into a number of monospecific and polyspecific clades <cite>Aspeborg2012</cite>. It should be noted that enzymes specifically targeting xylans are exclusively arabinoxylanases, and are found in subfamilies GH_21 <cite>Dodd2010</cite> and GH_34 <cite>Correia2011</cite>. Likewise, the GH5 predominant endo-xyloglucanases can be only observed in the subfamily GH_4 <cite>Attia2016, Aspeborg2012</cite>.
 == Kinetics and Mechanism ==
@@ Line 44: / Line 44: @@
 By analogy with family [[GH26]] mannnanases <cite>Ducros</cite> and family [[GH2]] &beta;-mannosidases <cite>Tailford</cite> it would seem likely that GH5 mannanases use a different conformational itinerary to their glucosidase relatives, likely via a <sup>1</sup>''S''<sub>5</sub>-<sup>O</sup>''S''<sub>2</sub> glycosylation pathway and thus ''via'' a ''B''<sub>2,5</sub> (near) transition-state although direct evidence in this family is limited <cite>Vincent</cite>.  An interesting dissection of mannan-degrading enzyme systems has been provided by work in the Gilbert group on the diverse GH5 and [[GH26]] mannanases in ''Cellvibrio japonicus''(see for example <cite>Hogg,Tailford-2 Cartmell2008</cite>).
-Within the huge functional diversity of the GH5 family, the GH5 subfamily 4 (GH5_4) is the only subfamily which was found to contain predominant endo-xyloglucanases <cite>Attia2016, Aspeborg2012</cite>. Although the GH5_4 endo-xyloglucanases share amino acid identity as low as 30%, the exhibited strict substrate specificity is ultimately attributed to the high conservation of the amino acid residues interacting with the xyloglucan substrate in the active site cleft <cite>Attia2018</cite>.
+The strict GH5_4 endo-xyloglucanases possess a wide active-site cleft that uniquely recognize the xylosyl substitutions of the polymeric substrate via discrete aromatic and hydrogen bond interactions. This is indeed contrary to the strict GH5 endo-glucanases which display a tight constriction in their active-site clefts leading to the apparent incapability of accommodating the highly branched xyloglucan substrate <cite>Naas2015</cite>. Notably, most of the GH5_4 endo-xyloglucanases cleave at the unbranched glucosyl units of the backbone due to the displayed constricted subsite -1 adjacent to the catalytic residues. Widening of that subsite, as observed in one of bovine rumen Gh5_4 endoxyloglucanase, can definitely confer the capability of cleavage at the substituted ''X'' unit leading to a different cleavage pattern <cite>dos santos2015</cite>.
 The GH5_34 enzymes target arabinoxylan through essential interactions with single arabinose substituents linked O3 to the xylose positioned in the active site -1 subsite <cite>Correia2011,Labourel2016</cite>. Very limited interactions with the xylan backbone is observed out with the -1 active site of the GH5_34 enzymes <cite>Labourel2016</cite>. This explains why these glycoside hydrolases cleave highly decorated glucuronoarabinoxylans that are recalcitrant to cleavage by classical xylanases found in GH10 and GH11.
@@ Line 60: / Line 60: @@
 == References ==
 <biblio>
 #Jenkins1995 pmid=7729513
 #Henrissat1995 pmid=7624375

@@ Line 35: / Line 35: @@
 == Catalytic Residues ==
-GH5 enzymes use the [[classical Koshland double-displacement mechanism]] and the two catalytic residues ([[catalytic nucleophile]] and [[general acid/base]]) are known to be glutamates found at the C-terminal ends of β-strands 4 (acid/base) and 7 (nucleophile) <cite>Henrissat1995 Henrissat1996 Jenkins1995</cite>.
+GH5 enzymes use the [[classical Koshland double-displacement mechanism]] and the two catalytic residues ([[catalytic nucleophile]] and [[general acid/base]]) are known to be glutamates found at the C-terminal ends of β-strands 4 (acid/base) and 7 (nucleophile) <cite>Henrissat1995 Jenkins1995</cite>.
 == Three-dimensional structures ==
-Three-dimensional structures are available for a very large number of Family GH5 enzymes, the first solved being that of the ''Clostridium thermocellum'' endoglucanase CelC <cite>Alzari1995</cite>. As members of [[Clan]] GH-A they have a classical (α/β)<sub>8</sub> TIM barrel fold with the two key active site glutamic acids being approximately 200 residues apart in sequence and located at the C-terminal ends of β-strands 4 (acid/base) and 7 (nucleophile) <cite>Henrissat1996 Jenkins1995</cite>.
+Three-dimensional structures are available for a very large number of Family GH5 enzymes, the first solved being that of the ''Clostridium thermocellum'' endoglucanase CelC <cite>Alzari1995</cite>. As members of [[Clan]] GH-A they have a classical (α/β)<sub>8</sub> TIM barrel fold with the two key active site glutamic acids being approximately 200 residues apart in sequence and located at the C-terminal ends of β-strands 4 (acid/base) and 7 (nucleophile) <cite>Henrissat1995 Jenkins1995</cite>.
 With so many 3D structures in this family, covering many specificities it is clearly hard to pick out notable structural papers.  The ''Bacillus agaradhaerens'' Cel5A has been extensively studied, notably in the trapping of enzymatic snapshots along the reaction coordinate <cite>Davies1998</cite> but also as a testbed for glycosidase inhibitor design as crystals often diffract to atomic resolution (for example <cite>Varrot2003</cite>).  The reaction coordinate work on the endoglucanases (thus working on ''gluco''-configured substrates) shows that the substrate binds in <sup>1</sup>S<sub>3</sub> conformation with the glycosyl enzyme [[intermediate]] in <sup>4</sup>''C''<sub>1</sub> chair conformation implying catalysis via a near <sup>4</sup>''H''<sub>3</sub> half-chair [[transition state]].
@@ Line 62: / Line 62: @@
 #Jenkins1995 pmid=7729513
 #Henrissat1995 pmid=7624375
 #Caines2007 pmid=17329247
 #Barras1992 pmid=1563515

@@ Line 43: / Line 43: @@
 By analogy with family [[GH26]] mannnanases <cite>Ducros</cite> and family [[GH2]] &beta;-mannosidases <cite>Tailford</cite> it would seem likely that GH5 mannanases use a different conformational itinerary to their glucosidase relatives, likely via a <sup>1</sup>''S''<sub>5</sub>-<sup>O</sup>''S''<sub>2</sub> glycosylation pathway and thus ''via'' a ''B''<sub>2,5</sub> (near) transition-state although direct evidence in this family is limited <cite>Vincent</cite>.  An interesting dissection of mannan-degrading enzyme systems has been provided by work in the Gilbert group on the diverse GH5 and [[GH26]] mannanases in ''Cellvibrio japonicus''(see for example <cite>Hogg,Tailford-2 Cartmell2008</cite>).
 The GH5_34 enzymes target arabinoxylan through essential interactions with single arabinose substituents linked O3 to the xylose positioned in the active site -1 subsite <cite>Correia2011,Labourel2016</cite>. Very limited interactions with the xylan backbone is observed out with the -1 active site of the GH5_34 enzymes <cite>Labourel2016</cite>. This explains why these glycoside hydrolases cleave highly decorated glucuronoarabinoxylans that are recalcitrant to cleavage by classical xylanases found in GH10 and GH11.
@@ Line 73: / Line 75: @@
 #Tailford-2 pmid=19441796
 #Hogg pmid=12523937
 #Vincent pmid=15515081
 #Cartmell2008 pmid=18799462

@@ Line 29: / Line 29: @@
 == Substrate specificities ==
-GH5 is one of the largest of all CAZy [[glycoside hydrolase]] families. Previously known as "cellulase family A" <cite>Henrissat1989 Gilkes1991</cite>, a variety of specificities are now known in this family, notably endoglucanase (cellulase) and endomannanase, as well as exoglucanases, exomannanases and β-glucosidase and β-mannosidase. Other activities include 1,6-galactanase, 1,3-mannanase, 1,4-xylanase, endoglycoceramidase, as well as high specificity xyloglucanases. Family GH5 enzymes are found widely distributed across Archae, bacteria and eukaryotes, notably fungi and plants. There are no known human enzymes in GH5.  Following the reclassification of a number of GH5 members into [[GH30]] <cite>StJohn2010</cite>, a GH5 subfamily classification has been presented that delineates members into a number of monospecific and polyspecific clades <cite>Aspeborg2012</cite>. It should be noted that enzymes specifically targeting xylans are exclusively arabinoxylanases, and are found in subfamilies GH_21 <cite>Dodd2010</cite> and GH_34 <cite>Correia2011</cite>. A similar subfamily classification was previously devised for [[GH13]] to aid functional prediction <cite>Stam2006</cite>.
+GH5 is one of the largest of all CAZy [[glycoside hydrolase]] families. Previously known as "cellulase family A" <cite>Henrissat1989 Gilkes1991</cite>, a variety of specificities are now known in this family, notably endoglucanase (cellulase) and endomannanase, as well as exoglucanases, exomannanases and β-glucosidase and β-mannosidase. Other activities include 1,6-galactanase, 1,3-mannanase, 1,4-xylanase, endoglycoceramidase, as well as high specificity xyloglucanases. Family GH5 enzymes are found widely distributed across Archae, bacteria and eukaryotes, notably fungi and plants. There are no known human enzymes in GH5.  Following the reclassification of a number of GH5 members into [[GH30]] <cite>StJohn2010</cite>, a GH5 subfamily classification has been presented that delineates members into a number of monospecific and polyspecific clades <cite>Aspeborg2012</cite>. It should be noted that enzymes specifically targeting xylans are exclusively arabinoxylanases, and are found in subfamilies GH_21 <cite>Dodd2010</cite> and GH_34 <cite>Correia2011</cite>.
 == Kinetics and Mechanism ==
@@ Line 56: / Line 56: @@
 ;First 3-D structure: The first 3D structures in family GH5 was an endoglucanase (cellulase) from ''Clostridium thermocellum'' reported by the Alzari in 1995 (in a paper which also reported a family GH10 xylanase structure and the similarities between them)  <cite>Dominguez1995</cite>. Subsequently, Ducros and colleagues reported the ''Clostridium cellulolyticum'' Cel5A also in 1995 <cite>Ducros1995</cite>.
-=== References ==
+== References ==
 <biblio>
 #Jenkins1995 pmid=7729513
@@ Line 78: / Line 78: @@
 #StJohn2010 pmid=20932833
 #Henrissat1989 pmid=2806912
 #Dodd2010 pmid=20622018
 #Correia2011 pmid=21378160