Glycoside Hydrolase Family 92 - Revision history

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

2021-12-18T21:19:20Z

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

Spencer Williams: /* Catalytic Residues */

2012-11-28T01:16:54Z

Catalytic Residues

Harry Brumer: fixed Tiels Biblio reference for consistency

2012-11-26T22:34:13Z

fixed Tiels Biblio reference for consistency

Spencer Williams at 22:00, 26 November 2012

2012-11-26T22:00:25Z

Spencer Williams at 22:00, 26 November 2012

2012-11-26T22:00:06Z

Spencer Williams: /* Three-dimensional structures */

2012-11-26T21:59:36Z

Three-dimensional structures

Spencer Williams: /* Catalytic Residues */

2012-11-26T21:58:48Z

Catalytic Residues

Spencer Williams: /* Kinetics and Mechanism */

2012-11-26T21:58:09Z

Kinetics and Mechanism

Spencer Williams at 21:56, 26 November 2012

2012-11-26T21:56:24Z

Spencer Williams at 21:55, 26 November 2012

2012-11-26T21:55:22Z

@@ Line 1: / Line 1: @@
 {{CuratorApproved}}
-* [[Author]]: ^^^Harry Gilbert^^^, ^^^Spencer Williams^^^
+* [[Author]]: [[User:Harry Gilbert|Harry Gilbert]], [[User:Spencer Williams|Spencer Williams]]
-* [[Responsible Curator]]:  ^^^Harry Gilbert^^^
+* [[Responsible Curator]]:  [[User:Harry Gilbert|Harry Gilbert]]
 ----

@@ Line 34: / Line 34: @@
 == Catalytic Residues ==
-Based on 3D structural data on the &alpha;-1,2-mannosidase Bt3990, Glu533 is the predicted [[general acid]]. This view is supported by an inactive mutant of this residue, and the conservation of the glutamate throughout the GH92 family <cite>Zhu2010</cite>. The [[general base]], in common with many [[inverting]] [[glycoside hydrolases]], is more difficult to identify. Asp644 and Asp642 both lie in the canonical position expected for a [[general base]] in an inverting enzyme. Mutants of either residues inactivate the enzyme, however, while Asp644 is invariant, Asp642 can be an Asn or Asp in GH92 members <cite>Zhu2010</cite>. It appears that Asp644 is the likely catalytic [[general base]]. In the case of the mannose-1-phosphate-6-mannoside cleaving &alpha;-mannosidase CcGH92_5 from ''Cellulosimicrobium cellulans'', the enzyme lacks the typical glutamic acid [[general acid]], which is replaced with a glutamine (Q536), which is not a proton donor <cite>Tiels2012</cite>. The phosphate group of the substrate is a much better leaving group than a typical glycoside, and it seems likely that this does not require [[general acid]] catalysis, similar to the case seen for plant myrosinases of family [[GH1]].
+Based on 3D structural data on the &alpha;-1,2-mannosidase Bt3990, Glu533 is the predicted [[general acid]]. This view is supported by an inactive mutant of this residue, and the conservation of the glutamate throughout the GH92 family <cite>Zhu2010</cite>. The [[general base]], in common with many [[inverting]] [[glycoside hydrolases]], is more difficult to identify. Asp644 and Asp642 both lie in the canonical position expected for a [[general base]] in an inverting enzyme. Mutants of either residues inactivate the enzyme, however, while Asp644 is invariant, Asp642 can be an Asn or Asp in GH92 members <cite>Zhu2010</cite>. It appears that Asp644 is the likely catalytic [[general base]]. In the case of the mannose-1-phosphate-6-mannoside cleaving &alpha;-mannosidase CcGH92_5 from ''Cellulosimicrobium cellulans'', the enzyme lacks the typical glutamic acid [[general acid]], which is replaced with a glutamine (Q536), which is not a proton donor <cite>Tiels2012</cite>. The phosphate group of the substrate is a much better leaving group than a typical glycoside, and it seems likely that this does not require [[general acid]] catalysis, similar to the case seen for plant myrosinases of family [[GH1]]. As well, the replacement of the glutamic acid with glutamine may reduce charge repulsion in the active site with the anionic phosphate aglycon.
 == Three-dimensional structures ==

@@ Line 28: / Line 28: @@
 == Substrate specificities ==
-The [[glycoside hydrolases]] of GH92 are [[exo]]-acting &alpha;-mannosidases. The first reported enzyme activity from this family was an &alpha;-1,2-mannosidase from ''Microbacterium'' sp. M-90 <cite>Maruyama1994</cite>. Zhu ''et al.'' reported the characterization of 22 GH92 enzymes from ''Bacteroides thetaiotaomicron'' and confirmed an [[exo]]-mode of action with &alpha;-1,2-mannosidase, &alpha;-1,3-mannosidase, &alpha;-1,4-mannosidase and &alpha;-1,6-mannosidase activities detected <cite>Zhu2010</cite>. Tiels ''et al.'' identified a subset of GH92 enzymes, typified by CcGH92_5 from ''Cellulosimicrobium cellulans'' (formerly ''Arthrobacter luteus'') that act to cleave yeast cell wall type mannose-1-phosphate-6-mannosides that are attached through N-linked core glycans to glycoproteins, releasing phosphate-6-mannosides (mannose-6-phosphate groups) <cite>Tiels</cite>. This subfamily of mannose-1-phosphate active enzymes do not act on typical &alpha;-mannosides, which has been attributed to the replacement of the catalytic [[general acid]] (glutamic acid) with a glutamine, and other amino acids that define a phosphate binding site <cite>Tiels</cite>.
+The [[glycoside hydrolases]] of GH92 are [[exo]]-acting &alpha;-mannosidases. The first reported enzyme activity from this family was an &alpha;-1,2-mannosidase from ''Microbacterium'' sp. M-90 <cite>Maruyama1994</cite>. Zhu ''et al.'' reported the characterization of 22 GH92 enzymes from ''Bacteroides thetaiotaomicron'' and confirmed an [[exo]]-mode of action with &alpha;-1,2-mannosidase, &alpha;-1,3-mannosidase, &alpha;-1,4-mannosidase and &alpha;-1,6-mannosidase activities detected <cite>Zhu2010</cite>. Tiels ''et al.'' identified a subset of GH92 enzymes, typified by CcGH92_5 from ''Cellulosimicrobium cellulans'' (formerly ''Arthrobacter luteus'') that act to cleave yeast cell wall type mannose-1-phosphate-6-mannosides that are attached through N-linked core glycans to glycoproteins, releasing phosphate-6-mannosides (mannose-6-phosphate groups) <cite>Tiels2012</cite>. This subfamily of mannose-1-phosphate active enzymes do not act on typical &alpha;-mannosides, which has been attributed to the replacement of the catalytic [[general acid]] (glutamic acid) with a glutamine, and other amino acids that define a phosphate binding site <cite>Tiels2012</cite>.
 == Kinetics and Mechanism ==
@@ Line 34: / Line 34: @@
 == Catalytic Residues ==
-Based on 3D structural data on the &alpha;-1,2-mannosidase Bt3990, Glu533 is the predicted [[general acid]]. This view is supported by an inactive mutant of this residue, and the conservation of the glutamate throughout the GH92 family <cite>Zhu2010</cite>. The [[general base]], in common with many [[inverting]] [[glycoside hydrolases]], is more difficult to identify. Asp644 and Asp642 both lie in the canonical position expected for a [[general base]] in an inverting enzyme. Mutants of either residues inactivate the enzyme, however, while Asp644 is invariant, Asp642 can be an Asn or Asp in GH92 members <cite>Zhu2010</cite>. It appears that Asp644 is the likely catalytic [[general base]]. In the case of the mannose-1-phosphate-6-mannoside cleaving &alpha;-mannosidase CcGH92_5 from ''Cellulosimicrobium cellulans'', the enzyme lacks the typical glutamic acid [[general acid]], which is replaced with a glutamine (Q536), which is not a proton donor <cite>Tiels</cite>. The phosphate group of the substrate is a much better leaving group than a typical glycoside, and it seems likely that this does not require [[general acid]] catalysis, similar to the case seen for plant myrosinases of family [[GH1]].
+Based on 3D structural data on the &alpha;-1,2-mannosidase Bt3990, Glu533 is the predicted [[general acid]]. This view is supported by an inactive mutant of this residue, and the conservation of the glutamate throughout the GH92 family <cite>Zhu2010</cite>. The [[general base]], in common with many [[inverting]] [[glycoside hydrolases]], is more difficult to identify. Asp644 and Asp642 both lie in the canonical position expected for a [[general base]] in an inverting enzyme. Mutants of either residues inactivate the enzyme, however, while Asp644 is invariant, Asp642 can be an Asn or Asp in GH92 members <cite>Zhu2010</cite>. It appears that Asp644 is the likely catalytic [[general base]]. In the case of the mannose-1-phosphate-6-mannoside cleaving &alpha;-mannosidase CcGH92_5 from ''Cellulosimicrobium cellulans'', the enzyme lacks the typical glutamic acid [[general acid]], which is replaced with a glutamine (Q536), which is not a proton donor <cite>Tiels2012</cite>. The phosphate group of the substrate is a much better leaving group than a typical glycoside, and it seems likely that this does not require [[general acid]] catalysis, similar to the case seen for plant myrosinases of family [[GH1]].
 == Three-dimensional structures ==
-GH92 enzymes display a two domain structure. The small N-terminal domain is a &beta;-sandwich and the large C-terminal domain adopts a adorned (&alpha;/&alpha;)<sub>6</sub> barrel fold. Amino acids in the active site of the enzyme, a shallow pocket, are contributed by both the N- and C-terminal domains <cite>Zhu2010</cite>. In complexes with inhibitors such as swainsonine, kifunensine, mannoimidazole, and deoxymannojirimycin the Ca<sup>2+</sup> ion is coordinated to the 2- and 3-OH groups of the inhibitors <cite>Zhu2010 Tiels</cite>.
+GH92 enzymes display a two domain structure. The small N-terminal domain is a &beta;-sandwich and the large C-terminal domain adopts a adorned (&alpha;/&alpha;)<sub>6</sub> barrel fold. Amino acids in the active site of the enzyme, a shallow pocket, are contributed by both the N- and C-terminal domains <cite>Zhu2010</cite>. In complexes with inhibitors such as swainsonine, kifunensine, mannoimidazole, and deoxymannojirimycin the Ca<sup>2+</sup> ion is coordinated to the 2- and 3-OH groups of the inhibitors <cite>Zhu2010 Tiels2012</cite>.
 == Family Firsts ==
@@ Line 49: / Line 49: @@
 #Maruyama1994 pmid=8149382
 #Zhu2010 pmid=20081828
-#Tiels pmid=23159880
+#Tiels2012 pmid=23159880
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH092]]

@@ Line 17: / Line 17: @@
 |-
 |'''Active site residues'''
-|known/not known
+|known
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''

@@ Line 1: / Line 1: @@
 {{CuratorApproved}}
-* [[Author]]: ^^^Harry Gilbert^^^
+* [[Author]]: ^^^Harry Gilbert^^^, ^^^Spencer Williams^^^
 * [[Responsible Curator]]:  ^^^Harry Gilbert^^^
 ----

@@ Line 31: / Line 31: @@
 == Kinetics and Mechanism ==
-<sup>1</sup>H NMR studies on three GH92s that displayed &alpha;-1,2-, &alpha;-1,3- and &alpha;-1,4-mannosidase activities all generated &beta;-mannose indicating that these enzymes catalyse glycosidic bond hydrolysis through a single displacement mechanism leading to [[inverting|inversion]] of anomeric configuration <cite>Zhu2010</cite>. GH92 enzymes are Ca<sup>2+</sup>-dependent &alpha;-mannosidases. The requirement for the metal ion is currently restricted to only three GH families all of which are [[exo]]-&alpha;-mannosidases: [[GH38]], [[GH47]] and GH92. Mechanistically this may indicate that the lack of distorting binding energy provided by the -2 or +1 subsites impose a requirement for conformational flexibility at the -1 subsite (recognition of the ground state and the [[transition state]] conformations), which is achieved by a metal ion interaction with O2 and O3. Three inhibitors bound to the &alpha;-1,2-mannosidase Bt3990 in approximate <sup>1</sup>''S''<sub>5</sub>/''B''<sub>2,5</sub> and <sup>1,4</sup>''B''/<sup>1</sup>''S''<sub>5</sub> conformations indicating that catalysis is proceeds via a ''B''<sub>2,5</sub>[[transition state]].
+<sup>1</sup>H NMR studies on three GH92s that displayed &alpha;-1,2-, &alpha;-1,3- and &alpha;-1,4-mannosidase activities all generated &beta;-mannose indicating that these enzymes catalyse glycosidic bond hydrolysis through a single displacement mechanism leading to [[inverting|inversion]] of anomeric configuration <cite>Zhu2010</cite>. GH92 enzymes are Ca<sup>2+</sup>-dependent &alpha;-mannosidases. The requirement for the metal ion is currently restricted to only three GH families all of which are [[exo]]-&alpha;-mannosidases: [[GH38]], [[GH47]] and GH92. Mechanistically this may indicate that the lack of distorting binding energy provided by the -2 or +1 subsites impose a requirement for conformational flexibility at the -1 subsite (recognition of the ground state and the [[transition state]] conformations), which is achieved by a metal ion interaction with O2 and O3. Three inhibitors bound to the &alpha;-1,2-mannosidase Bt3990 in approximate <sup>1</sup>''S''<sub>5</sub>/''B''<sub>2,5</sub> and <sup>1,4</sup>''B''/<sup>1</sup>''S''<sub>5</sub> conformations indicating that catalysis is proceeds via a ''B''<sub>2,5</sub> [[transition state]].
 == Catalytic Residues ==

@@ Line 28: / Line 28: @@
 == Substrate specificities ==
-The [[glycoside hydrolases]] of GH92 are [[exo]]-acting &alpha;-mannosidases. The first reported enzyme activity from this family was an &alpha;-1,2-mannosidase from ''Microbacterium'' sp. M-90 <cite>#1</cite>. Zhu ''et al.'' reported the characterization of 22 GH92 enzymes from ''Bacteroides thetaiotaomicron'' and confirmed an [[exo]]-mode of action with &alpha;-1,2-mannosidase, &alpha;-1,3-mannosidase, &alpha;-1,4-mannosidase and &alpha;-1,6-mannosidase activities detected <cite>#2</cite>. Tiels ''et al.'' identified a subset of GH92 enzymes, typified by CcGH92_5 from ''Cellulosimicrobium cellulans'' (formerly ''Arthrobacter luteus'') that act to cleave yeast cell wall type mannose-1-phosphate-6-mannosides that are attached through N-linked core glycans to glycoproteins, releasing phosphate-6-mannosides (mannose-6-phosphate groups) <cite>Tiels</cite>. This subfamily of mannose-1-phosphate active enzymes do not act on typical &alpha;-mannosides, which has been attributed to the replacement of the catalytic [[general acid]] (glutamic acid) with a glutamine, and other amino acids that define a phosphate binding site <cite>Tiels</cite>.
+The [[glycoside hydrolases]] of GH92 are [[exo]]-acting &alpha;-mannosidases. The first reported enzyme activity from this family was an &alpha;-1,2-mannosidase from ''Microbacterium'' sp. M-90 <cite>#1</cite>. Zhu ''et al.'' reported the characterization of 22 GH92 enzymes from ''Bacteroides thetaiotaomicron'' and confirmed an [[exo]]-mode of action with &alpha;-1,2-mannosidase, &alpha;-1,3-mannosidase, &alpha;-1,4-mannosidase and &alpha;-1,6-mannosidase activities detected <cite>Zhu2010</cite>. Tiels ''et al.'' identified a subset of GH92 enzymes, typified by CcGH92_5 from ''Cellulosimicrobium cellulans'' (formerly ''Arthrobacter luteus'') that act to cleave yeast cell wall type mannose-1-phosphate-6-mannosides that are attached through N-linked core glycans to glycoproteins, releasing phosphate-6-mannosides (mannose-6-phosphate groups) <cite>Tiels</cite>. This subfamily of mannose-1-phosphate active enzymes do not act on typical &alpha;-mannosides, which has been attributed to the replacement of the catalytic [[general acid]] (glutamic acid) with a glutamine, and other amino acids that define a phosphate binding site <cite>Tiels</cite>.
 == Kinetics and Mechanism ==
-<sup>1</sup>H NMR studies on three GH92s that displayed &alpha;-1,2-, &alpha;-1,3- and &alpha;-1,4-mannosidase activities all generated &beta;-mannose indicating that these enzymes catalyse glycosidic bond hydrolysis through a single displacement mechanism leading to [[inverting|inversion]] of anomeric configuration <cite>#2</cite>. GH92 enzymes are Ca<sup>2+</sup>-dependent &alpha;-mannosidases. The requirement for the metal ion is currently restricted to only three GH families all of which are [[exo]]-&alpha;-mannosidases: [[GH38]], [[GH47]] and GH92. Mechanistically this may indicate that the lack of distorting binding energy provided by the -2 or +1 subsites impose a requirement for conformational flexibility at the -1 subsite (recognition of the ground state and the [[transition state]] conformations), which is achieved by a metal ion interaction with O2 and O3. Three inhibitors bound to the &alpha;-1,2-mannosidase Bt3990 in approximate <sup>1</sup>''S''<sub>5</sub>/''B''<sub>2,5</sub> and <sup>1,4</sup>''B''/<sup>1</sup>''S''<sub>5</sub> conformations indicating that catalysis is proceeds via a ''B''<sub>2,5</sub>[[transition state]].
+<sup>1</sup>H NMR studies on three GH92s that displayed &alpha;-1,2-, &alpha;-1,3- and &alpha;-1,4-mannosidase activities all generated &beta;-mannose indicating that these enzymes catalyse glycosidic bond hydrolysis through a single displacement mechanism leading to [[inverting|inversion]] of anomeric configuration <cite>Zhu2010</cite>. GH92 enzymes are Ca<sup>2+</sup>-dependent &alpha;-mannosidases. The requirement for the metal ion is currently restricted to only three GH families all of which are [[exo]]-&alpha;-mannosidases: [[GH38]], [[GH47]] and GH92. Mechanistically this may indicate that the lack of distorting binding energy provided by the -2 or +1 subsites impose a requirement for conformational flexibility at the -1 subsite (recognition of the ground state and the [[transition state]] conformations), which is achieved by a metal ion interaction with O2 and O3. Three inhibitors bound to the &alpha;-1,2-mannosidase Bt3990 in approximate <sup>1</sup>''S''<sub>5</sub>/''B''<sub>2,5</sub> and <sup>1,4</sup>''B''/<sup>1</sup>''S''<sub>5</sub> conformations indicating that catalysis is proceeds via a ''B''<sub>2,5</sub>[[transition state]].
 == Catalytic Residues ==
-Based on 3D structural data on the &alpha;-1,2-mannosidase Bt3990, Glu533 is the predicted [[general acid]]. This view is supported by an inactive mutant of this residue, and the conservation of the glutamate throughout the GH92 family <cite>#2</cite>. The [[general base]], in common with many [[inverting]] [[glycoside hydrolases]], is more difficult to identify. Asp644 and Asp642 both lie in the canonical position expected for a [[general base]] in an inverting enzyme. Mutants of either residues inactivate the enzyme, however, while Asp644 is invariant, Asp642 can be an Asn or Asp in GH92 members <cite>#2</cite>. It appears that Asp644 is the likely catalytic [[general base]]. In the case of the mannose-1-phosphate-6-mannoside cleaving &alpha;-mannosidase CcGH92_5 from ''Cellulosimicrobium cellulans'', the enzyme lacks the typical glutamic acid [[general acid]], which is replaced with a glutamine (Q536), which is not a proton donor <cite>Tiels</cite>. The phosphate group of the substrate is a much better leaving group than a typical glycoside, and it seems likely that this does not require [[general acid]] catalysis, similar to the case seen for myrosinases of family [[GH1]].
+Based on 3D structural data on the &alpha;-1,2-mannosidase Bt3990, Glu533 is the predicted [[general acid]]. This view is supported by an inactive mutant of this residue, and the conservation of the glutamate throughout the GH92 family <cite>#2</cite>. The [[general base]], in common with many [[inverting]] [[glycoside hydrolases]], is more difficult to identify. Asp644 and Asp642 both lie in the canonical position expected for a [[general base]] in an inverting enzyme. Mutants of either residues inactivate the enzyme, however, while Asp644 is invariant, Asp642 can be an Asn or Asp in GH92 members <cite>Zhu2010</cite>. It appears that Asp644 is the likely catalytic [[general base]]. In the case of the mannose-1-phosphate-6-mannoside cleaving &alpha;-mannosidase CcGH92_5 from ''Cellulosimicrobium cellulans'', the enzyme lacks the typical glutamic acid [[general acid]], which is replaced with a glutamine (Q536), which is not a proton donor <cite>Tiels</cite>. The phosphate group of the substrate is a much better leaving group than a typical glycoside, and it seems likely that this does not require [[general acid]] catalysis, similar to the case seen for myrosinases of family [[GH1]].
 == Three-dimensional structures ==
-GH92 enzymes display a two domain structure. The small N-terminal domain is a beta-sandwich and the large C-terminal domain adopts a adorned (alpha/alpha)6 barrel fold. Amino acids in the active site of the enzyme, a shallow pocket, are contributed by both the N- and C-terminal domains <cite>#2</cite>. In complexes with inhibitors such as swainsonine, kifunensine, mannoimidazole, and deoxymannojirimycin the Ca<sup>2+</sup> ion is seen coordinated to the 2- and 3-OH groups of the inhibitors <cite>#2 Tiels</cite>.
+GH92 enzymes display a two domain structure. The small N-terminal domain is a beta-sandwich and the large C-terminal domain adopts a adorned (alpha/alpha)6 barrel fold. Amino acids in the active site of the enzyme, a shallow pocket, are contributed by both the N- and C-terminal domains <cite>Zhu2010</cite>. In complexes with inhibitors such as swainsonine, kifunensine, mannoimidazole, and deoxymannojirimycin the Ca<sup>2+</sup> ion is seen coordinated to the 2- and 3-OH groups of the inhibitors <cite>#2 Tiels</cite>.
 == Family Firsts ==
-;First sterochemistry determination: <sup>1</sup>H NMR showed three GH92s generate &beta;-mannose and thus these &alpha;-mannosidases are [[inverting]] enzymes <cite>#2</cite>.
+;First sterochemistry determination: <sup>1</sup>H NMR showed three GH92s generate &beta;-mannose and thus these &alpha;-mannosidases are [[inverting]] enzymes <cite>Zhu2010</cite>.
-;First [[general acid]] identification: Based on mutagenesis and 3D structural information the conserved catalytic acid has been identified <cite>#2</cite>.
+;First [[general acid]] identification: Based on mutagenesis and 3D structural information the conserved catalytic acid has been identified <cite>Zhu2010</cite>.
-;First [[general base]] residue identification: Based on mutagenesis and 3D structural information a pair of likely catalytic bases were identified. As one of these residues is invariant this is the proposed catalytic base <cite>#2</cite>.
+;First [[general base]] residue identification: Based on mutagenesis and 3D structural information a pair of likely catalytic bases were identified. As one of these residues is invariant this is the proposed catalytic base <cite>Zhu2010</cite>.
-;First 3-D structure: The 3D structure reveals two domains; an N-terminal &beta;-sandwich domain and a C-terminal adorned (&alpha;/&alpha;)<sub>6</sub> barrel. Both domains contribute residues to the active site <cite>#2</cite>.
+;First 3-D structure: The 3D structure reveals two domains; an N-terminal &beta;-sandwich domain and a C-terminal adorned (&alpha;/&alpha;)<sub>6</sub> barrel. Both domains contribute residues to the active site <cite>Zhu2010</cite>.
 == References ==
 <biblio>
 #1 pmid=8149382
-#2 pmid=20081828
+#Zhu2010 pmid=20081828
-Tiels pmid=23159880
+#Tiels pmid=23159880
 ; http://dx.doi.org/10.1038/nchembio.278