Glycoside Hydrolase Family 116 - Revision history

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

2021-12-18T21:20:05Z

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

Harry Brumer: added DOI for Koshland ref.

2019-07-17T17:31:16Z

added DOI for Koshland ref.

Spencer Williams: /* Kinetics and Mechanism */

2016-05-08T12:38:17Z

Kinetics and Mechanism

Spencer Williams at 12:37, 8 May 2016

2016-05-08T12:37:43Z

Spencer Williams at 01:52, 5 May 2016

2016-05-05T01:52:13Z

Spencer Williams at 01:52, 5 May 2016

2016-05-05T01:52:02Z

Spencer Williams at 01:51, 5 May 2016

2016-05-05T01:51:16Z

Spencer Williams at 01:37, 5 May 2016

2016-05-05T01:37:09Z

Harry Brumer: changed biblio tages to AuthorYear format for easier page maintenance

2013-11-27T16:40:21Z

changed biblio tages to AuthorYear format for easier page maintenance

Harry Brumer: fixed paragraph indentation

2013-11-27T16:34:24Z

fixed paragraph indentation

@@ Line 1: / Line 1: @@
 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Beatrice Cobucci-Ponzano^^^, ^^^Spencer Williams^^^
+* [[Author]]: [[User:Beatrice Cobucci-Ponzano|Beatrice Cobucci-Ponzano]], [[User:Spencer Williams|Spencer Williams]]
-* [[Responsible Curator]]:  ^^^Marco Moracci^^^
+* [[Responsible Curator]]:  [[User:Marco Moracci|Marco Moracci]]
 ----

@@ Line 51: / Line 51: @@
 #Boot2007 pmid=17105727
 #Ferrara2013 pmid=24060745
-#Koshland1953 Koshland DE Jr: Stereochemistry and the mechanism of enzyme reactions. Biol Rev 1953, 28:416-436.
+#Koshland1953 Koshland DE Jr: Stereochemistry and the mechanism of enzyme reactions. Biol Rev 1953, 28:416-436. [https://doi.org/10.1111/j.1469-185X.1953.tb01386.x DOI:10.1111/j.1469-185X.1953.tb01386.x]
 #Charoenwattanasatien2016 pmid=27115290
 </biblio>

@@ Line 32: / Line 32: @@
 == Kinetics and Mechanism ==
-The enzymes of this family are ''[[retaining]]'' glycoside hydrolases and follow the classical [[Koshland double-displacement mechanism]] <cite>Koshland1953</cite>. The stereochemistry of hydrolysis has been demonstrated by <sup>1</sup>H-<sup>13</sup>C NMR spectroscopy analysis of the interglycosidic linkage of disaccharides formed by the transglycosylation reaction of SSO1353 with 4NP-β-Xyl <cite>CobucciPonzano2010</cite>, and by direct observation of the formation of β-glucose in the hydrolysis of PNP β-glucoside by ''Thermoanaerobacterium xylanolyticum'' ''Tx''GH116 β-glucosidase <cite>Charoenwattanasatien2016</cite>.
+The enzymes of this family are ''[[retaining]]'' glycoside hydrolases and follow the classical [[Koshland double-displacement mechanism]] <cite>Koshland1953</cite>. The stereochemistry of hydrolysis has been demonstrated by <sup>1</sup>H-<sup>13</sup>C NMR spectroscopy analysis of the interglycosidic linkage of disaccharides formed by the transglycosylation reaction of SSO1353 with 4NP-β-Xyl <cite>CobucciPonzano2010</cite>, and by direct observation of the formation of β-glucose in the hydrolysis of PNP β-glucoside by ''Thermoanaerobacterium xylanolyticum'' ''Tx''GH116 β-glucosidase by <sup>1</sup>H NMR spectroscopy <cite>Charoenwattanasatien2016</cite>.
 == Catalytic Residues ==

@@ Line 29: / Line 29: @@
 == Substrate specificities ==
-This family of [[glycoside hydrolases]] was discovered characterising a β-glycosidase from the hyperthermophilic archaeon ''Sulfolobus solfataricus'' <cite>CobucciPonzano2010</cite> and contains mammalian bile acid β-glucosidase (EC [{{EClink}}3.2.1.45 3.2.1.45], also known as glucosylceramidase, β-glucosidase (EC [{{EClink}}3.2.1.21 3.2.1.21]) and β-xylosidase (EC [{{EClink}}3.2.1.37 3.2.1.37]) activities from the three  domains of life. The β-glycosidase from ''S. solfataricus'' (SSO1353) is specific for the gluco- and xylosides β-bound to hydrophobic groups that are hydrolyzed by following a ''[[retaining]]'' reaction mechanism. Human non-lysosomal bile acid β-glucosidase GBA2, also known as glucocerebrosidase, is involved in the catabolism of glucosylceramide, which is then converted to sphingomyelin <cite>Boot2007</cite>. A β-N-acetylglucosaminidase from ''S. solfataricus'' (SSO3039) from the same family <cite>Ferrara2013</cite> was shown to act as a bifunctional β-glucosidase/β-''N''-acetylglucosaminidase. Phylogenetic analysis allowed classification of GH116 into three subfamilies <cite>Ferrara2013</cite>, each of which now has an enzyme characterized in detail: subfamily 1 contains GBA2 glucosylceramidase <cite>Boot2007</cite>, subfamily 2 includes SSO3039 <cite>Ferrara2013</cite>, and subfamily 3 contains SSO1353 <cite>CobucciPonzano2010</cite>. The three subfamilies are functionally different and are hypothesized to have evolved from a common ancestor. Common characteristics of family GH116 are the specificity for β-glucosides and the ''[[retaining]]'' reaction mechanism. However, subfamilies 1, 2, and 3, have also specificity for glucosylceramides, ''N''-acetyl-glucosaminides, and xylosides, respectively, and peculiar sensitivity to competitive inhibitors. In fact, GBA2 (subfamily 1) is insensitive to CBE and is inhibited by nM amounts of NB-DNJ <cite>Boot2007</cite>, SSO3039 (subfamily 2) is sensitive to μM and mM concentrations of NB-DNJ and CBE, respectively <cite>Ferrara2013</cite>, whilst SSO1353 (subfamily 3) shows mM sensitivity to both NB-DNJ and CBE <cite>CobucciPonzano2010</cite>.
+This family of [[glycoside hydrolases]] was discovered characterising a β-glycosidase from the hyperthermophilic archaeon ''Sulfolobus solfataricus'' <cite>CobucciPonzano2010</cite> and contains mammalian non-lysosomal bile acid β-glucosidase GBA2 (EC [{{EClink}}3.2.1.45 3.2.1.45], also known as glucosylceramidase), β-glucosidase (EC [{{EClink}}3.2.1.21 3.2.1.21]) and β-xylosidase (EC [{{EClink}}3.2.1.37 3.2.1.37]) activities from the three  domains of life. The β-glycosidase from ''S. solfataricus'' (SSO1353) is specific for the gluco- and xylosides β-bound to hydrophobic groups that are hydrolyzed by following a ''[[retaining]]'' reaction mechanism. Human non-lysosomal bile acid β-glucosidase GBA2, is involved in the catabolism of glucosylceramide, which is then converted to sphingomyelin <cite>Boot2007</cite>. A β-N-acetylglucosaminidase from ''S. solfataricus'' (SSO3039) from the same family <cite>Ferrara2013</cite> was shown to act as a bifunctional β-glucosidase/β-''N''-acetylglucosaminidase. Phylogenetic analysis allowed classification of GH116 into three subfamilies <cite>Ferrara2013</cite>, each of which now has an enzyme characterized in detail: subfamily 1 contains GBA2 glucosylceramidase <cite>Boot2007</cite>, subfamily 2 includes SSO3039 <cite>Ferrara2013</cite>, and subfamily 3 contains SSO1353 <cite>CobucciPonzano2010</cite>. The three subfamilies are functionally different and are hypothesized to have evolved from a common ancestor. Common characteristics of family GH116 are the specificity for β-glucosides and the ''[[retaining]]'' reaction mechanism. However, subfamilies 1, 2, and 3, have also specificity for glucosylceramides, ''N''-acetyl-glucosaminides, and xylosides, respectively, and peculiar sensitivity to competitive inhibitors. In fact, GBA2 (subfamily 1) is insensitive to CBE and is inhibited by nM amounts of NB-DNJ <cite>Boot2007</cite>, SSO3039 (subfamily 2) is sensitive to μM and mM concentrations of NB-DNJ and CBE, respectively <cite>Ferrara2013</cite>, whilst SSO1353 (subfamily 3) shows mM sensitivity to both NB-DNJ and CBE <cite>CobucciPonzano2010</cite>.
 == Kinetics and Mechanism ==
@@ Line 38: / Line 38: @@
 == Three-dimensional structures ==
-The structure of ''T. xylanolyticum'' ''Tx''GH116 β-glucosidase has been reported <cite>Charoenwattanasatien2016</cite>. This structure consists of an N-terminal domain, comprised of a two-sheet β-sandwich, and a C-terminal (α/α)<sub>6</sub> solenoid domain. The catalytic nucleophile and general acid/base are contained within the C-terminal domain. The putative catalytic nucleophile, E441, lies near the end of a loop between the first and second α-helices of the C-terminal domain; the putative catalytic acid/base, D593, lies in a loop between the fifth and sixth helices of the C-terminal domain. A Ca<sup>2+</sup> is bound to a site withing the same loop that contains the general acid/base.
+The structure of ''T. xylanolyticum'' ''Tx''GH116 β-glucosidase has been reported <cite>Charoenwattanasatien2016</cite>. This structure consists of an N-terminal domain, comprised of a two-sheet β-sandwich, and a C-terminal (α/α)<sub>6</sub> solenoid domain. The catalytic nucleophile and general acid/base are contained within the C-terminal domain. The putative catalytic nucleophile, E441, lies near the end of a loop between the first and second α-helices of the C-terminal domain; the putative catalytic acid/base, D593, lies in a loop between the fifth and sixth helices of the C-terminal domain. A Ca<sup>2+</sup> is bound to a site within the same loop that contains the general acid/base.
 == Family Firsts ==

@@ Line 1: / Line 1: @@
 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Beatrice Cobucci-Ponzano^^^ ^^^Spencer Williams^^^
+* [[Author]]: ^^^Beatrice Cobucci-Ponzano^^^, ^^^Spencer Williams^^^
 * [[Responsible Curator]]:  ^^^Marco Moracci^^^
 ----

@@ Line 12: / Line 12: @@
 |-
 |'''Clan'''
-| none
+| GH-O
 |-
 |'''Mechanism'''
@@ Line 29: / Line 29: @@
 == Substrate specificities ==
-This family of [[glycoside hydrolases]] was discovered characterising a β-glycosidase from the hyperthermophilic archaeon ''Sulfolobus solfataricus'' <cite>CobucciPonzano2010</cite> and contains acid β-glucosidase (EC [{{EClink}}3.2.1.45 3.2.1.45]), β-glucosidase (EC [{{EClink}}3.2.1.21 3.2.1.21]) and β-xylosidase (EC [{{EClink}}3.2.1.37 3.2.1.37]) activities from the three  domains of life. The β-glycosidase from ''S. solfataricus'' (SSO1353) is specific for the gluco- and xylosides β-bound to hydrophobic groups that are hydrolyzed by following a ''[[retaining]]'' reaction mechanism. SSO1353 is  distantly related to the human non-lysosomal bile acid β-glucosidase GBA2, also known as glucocerebrosidase, involved in the catabolism of glucosylceramide, which is then converted to sphingomyelin <cite>Boot2007</cite>. Recently, a new β-N-acetylglucosaminidase from S. solfataricus (SSO3039) from the same family <cite>Ferrara2013</cite> was characterized, demonstrating that it is a bifunctional β-glucosidase/β-N-acetylglucosaminidase. The phylogenetic analysis shows that GH116 can be separated in three subfamilies <cite>Ferrara2013</cite>, each of which now has an enzyme characterized in detail: subfamily 1 contains GBA2 <cite>Boot2007</cite>, subfamily 2 includes SSO3039 <cite>Ferrara2013</cite>, and subfamily 3 contains SSO1353 <cite>CobucciPonzano2010</cite>. The three subfamilies are functionally different and have evolved from a common ancestor. Common characteristics of family GH116 are the specificity for β-O-glucosides and the ''[[retaining]]'' reaction mechanism. However, subfamilies 1, 2, and 3, have also specificity for glucosylceramides, N-acetyl-glucosaminides, and xylosides, respectively, and peculiar sensitivity to competitive inhibitors. In fact, GBA2 (subfamily 1) is insensitive to CBE and is inhibited by nM amounts of NB-DNJ <cite>Boot2007</cite>, SSO3039 (subfamily 2) is sensitive to μM and mM concentrations of NB-DNJ and CBE, respectively <cite>Ferrara2013</cite>, whilst SSO1353 (subfamily 3) shows mM sensitivity to both NB-DNJ and CBE <cite>CobucciPonzano2010</cite>.
+This family of [[glycoside hydrolases]] was discovered characterising a β-glycosidase from the hyperthermophilic archaeon ''Sulfolobus solfataricus'' <cite>CobucciPonzano2010</cite> and contains mammalian acid β-glucosidase (EC [{{EClink}}3.2.1.45 3.2.1.45], also known as glucosylceramidase, β-glucosidase (EC [{{EClink}}3.2.1.21 3.2.1.21]) and β-xylosidase (EC [{{EClink}}3.2.1.37 3.2.1.37]) activities from the three  domains of life. The β-glycosidase from ''S. solfataricus'' (SSO1353) is specific for the gluco- and xylosides β-bound to hydrophobic groups that are hydrolyzed by following a ''[[retaining]]'' reaction mechanism. SSO1353 is  distantly related to the human non-lysosomal bile acid β-glucosidase GBA2, also known as glucocerebrosidase, involved in the catabolism of glucosylceramide, which is then converted to sphingomyelin <cite>Boot2007</cite>. Recently, a new β-N-acetylglucosaminidase from ''S. solfataricus'' (SSO3039) from the same family <cite>Ferrara2013</cite> was characterized, demonstrating that it is a bifunctional β-glucosidase/β-N-acetylglucosaminidase. The phylogenetic analysis shows that GH116 can be separated in three subfamilies <cite>Ferrara2013</cite>, each of which now has an enzyme characterized in detail: subfamily 1 contains GBA2 glucosylceramidase <cite>Boot2007</cite>, subfamily 2 includes SSO3039 <cite>Ferrara2013</cite>, and subfamily 3 contains SSO1353 <cite>CobucciPonzano2010</cite>. The three subfamilies are functionally different and have evolved from a common ancestor. Common characteristics of family GH116 are the specificity for β-glucosides and the ''[[retaining]]'' reaction mechanism. However, subfamilies 1, 2, and 3, have also specificity for glucosylceramides, ''N''-acetyl-glucosaminides, and xylosides, respectively, and peculiar sensitivity to competitive inhibitors. In fact, GBA2 (subfamily 1) is insensitive to CBE and is inhibited by nM amounts of NB-DNJ <cite>Boot2007</cite>, SSO3039 (subfamily 2) is sensitive to μM and mM concentrations of NB-DNJ and CBE, respectively <cite>Ferrara2013</cite>, whilst SSO1353 (subfamily 3) shows mM sensitivity to both NB-DNJ and CBE <cite>CobucciPonzano2010</cite>.
 == Kinetics and Mechanism ==
@@ Line 44: / Line 44: @@
 ;First catalytic nucleophile identification: ''S. solfataricus'' β-glycosidase  SSO1353 by 2-deoxy-2-fluoroglucose labeling <cite>CobucciPonzano2010</cite>.
 ;First general acid/base residue identification: ''S. solfataricus'' β-glycosidase SSO1353 by azide rescue with mutant <cite>CobucciPonzano2010</cite>.
-;First 3-D structure: Presently unknown (see [{{CAZyDBlink}}GH116.html GH116 at CAZy DB]).
+;First 3-D structure: ''Thermoanaerobacterium xylanolyticum'' ''Tx''GH116 β-glucosidase <cite>Charoenwattanasatien2016</cite>.
 == References ==
@@ Line 52: / Line 52: @@
 #Ferrara2013 pmid=24060745
 #Koshland1953 Koshland DE Jr: Stereochemistry and the mechanism of enzyme reactions. Biol Rev 1953, 28:416-436.
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH116]]

@@ Line 32: / Line 32: @@
 == Kinetics and Mechanism ==
-  The enzymes of this family are ''[[retaining]]'' glycoside hydrolases and follow the classical [[Koshland double-displacement mechanism]] <cite>Koshland</cite>. The stereochemistry of hydrolysis has been demonstrated by <sup>1</sup>H-<sup>13</sup>C NMR spectroscopy analysis of the interglycosidic linkage of disaccharides formed by the transglycosylation reaction of SSO1353 with 4NP-β-Xyl <cite>PMID20427274</cite>.
+The enzymes of this family are ''[[retaining]]'' glycoside hydrolases and follow the classical [[Koshland double-displacement mechanism]] <cite>Koshland</cite>. The stereochemistry of hydrolysis has been demonstrated by <sup>1</sup>H-<sup>13</sup>C NMR spectroscopy analysis of the interglycosidic linkage of disaccharides formed by the transglycosylation reaction of SSO1353 with 4NP-β-Xyl <cite>PMID20427274</cite>.
 == Catalytic Residues ==
-  The catalytic residues were identified in the ''S. solfataricus'' β-glycosidase SSO1353 <cite>PMID20427274</cite>. The [[catalytic nucleophile]] was identified as Glu335 through trapping of the 2-deoxy-2-fluoroglucosyl-enzyme [[intermediate]] and MS/MS analysis. The [[general acid/base]] catalyst role was assigned to Asp462 through mechanistic analysis of a mutant at that position, which included azide rescue experiments.
+The catalytic residues were identified in the ''S. solfataricus'' β-glycosidase SSO1353 <cite>PMID20427274</cite>. The [[catalytic nucleophile]] was identified as Glu335 through trapping of the 2-deoxy-2-fluoroglucosyl-enzyme [[intermediate]] and MS/MS analysis. The [[general acid/base]] catalyst role was assigned to Asp462 through mechanistic analysis of a mutant at that position, which included azide rescue experiments.
 == Three-dimensional structures ==
-  There is currently no 3-D structure representative for GH116 (see [{{CAZyDBlink}}GH116.html GH116 at CAZy DB]).
+There is currently no 3-D structure representative for GH116 (see [{{CAZyDBlink}}GH116.html GH116 at CAZy DB]).
 == Family Firsts ==
@@ Line 51: / Line 45: @@
 ;First general acid/base residue identification: ''S. solfataricus'' β-glycosidase SSO1353 by azide rescue with mutant <cite>PMID20427274</cite>.
 ;First 3-D structure: Presently unknown (see [{{CAZyDBlink}}GH116.html GH116 at CAZy DB]).
 == References ==