Glycoside Hydrolase Family 43 - Revision history

Harry Brumer: added ref. to subfamily classification paper

2024-09-26T21:49:00Z

added ref. to subfamily classification paper

Spencer Williams: /* Kinetics and Mechanism */

2017-03-27T22:36:57Z

Kinetics and Mechanism

Harry Gilbert at 14:52, 5 August 2016

2016-08-05T14:52:32Z

Harry Brumer: Updated reference tags to standard format

2016-08-03T17:53:02Z

Updated reference tags to standard format

Harry Gilbert: /* Catalytic Residues */

2016-08-02T09:05:06Z

Catalytic Residues

Harry Gilbert: /* Catalytic Residues */

2016-08-02T09:03:52Z

Catalytic Residues

Harry Brumer: updated CAZyDBlink

2012-09-10T16:37:19Z

updated CAZyDBlink

Spencer Williams at 03:08, 14 June 2011

2011-06-14T03:08:29Z

Harry Gilbert at 16:29, 29 September 2010

2010-09-29T16:29:43Z

Spencer Williams at 01:16, 5 September 2010

2010-09-05T01:16:30Z

@@ Line 26: / Line 26: @@
 == Substrate specificities ==
-The major activities reported for this family of [[glycoside hydrolases]] are &alpha;-L-arabinofuranosidases <cite>Flipphi1993a</cite>, [[endo]]-&alpha;-L-arabinanases (or endo-processive arabinanases) <cite>McKie1997 Flipphi1993b</cite> and &beta;-D-xylosidases <cite>Shallom2005</cite> (for further details see: [[Absolute configuration: D/L nomenclature]]). An enzyme with [[exo]] &alpha;-1,3-galactanase has also been described <cite>Ichinose2005</cite>. A significant number of enzymes in this family display both &alpha;-L-arabinofuranosidase and &beta;-D-xylosidase activity using aryl-glycosides as substrates. It is likely that the natural activity of these enzymes is conferred by the leaving-group component of the substrate. Indeed, the arabionofuranosidase activities already reported target very different glycans. Thus, the ''Bacillus subtilis'' enzyme arabinoxylan &alpha;-L-arabinofuranohydrolase specifically removes arabinofuranose side chains that are linked either &alpha;-1,2 or &alpha;-1,3  to backbone xylose residues <cite>Bourgois2007</cite>, while the arabinoxylan arabinofuranohydrolase-D3 (AXHd3) from ''Bifidobacterium adolescentis'' will remove an &alpha;-1,3-linked arabinofuranose from xylans where the xylose residue is substituted at both &alpha;-1,2 and &alpha;-1,3  with arabinose <cite>vandenBroek2005</cite>. By contrast some arabinofuranosidases are [[exo]]-&alpha;-1,5-L-arabinanases <cite>Matsuo2000</cite>. It should be noted that in several plant cell wall degrading organisms there has been a dramatic expansion in GH43 family enzymes, which may reflect a more extensive range of specificities than described to date.
+The major activities reported for this family of [[glycoside hydrolases]] are &alpha;-L-arabinofuranosidases <cite>Flipphi1993a</cite>, [[endo]]-&alpha;-L-arabinanases (or endo-processive arabinanases) <cite>McKie1997 Flipphi1993b</cite> and &beta;-D-xylosidases <cite>Shallom2005</cite> (for further details see: [[Absolute configuration: D/L nomenclature]]). An enzyme with [[exo]] &alpha;-1,3-galactanase has also been described <cite>Ichinose2005</cite>. A significant number of enzymes in this family display both &alpha;-L-arabinofuranosidase and &beta;-D-xylosidase activity using aryl-glycosides as substrates. It is likely that the natural activity of these enzymes is conferred by the leaving-group component of the substrate. Indeed, the arabionofuranosidase activities already reported target very different glycans. Thus, the ''Bacillus subtilis'' enzyme arabinoxylan &alpha;-L-arabinofuranohydrolase specifically removes arabinofuranose side chains that are linked either &alpha;-1,2 or &alpha;-1,3  to backbone xylose residues <cite>Bourgois2007</cite>, while the arabinoxylan arabinofuranohydrolase-D3 (AXHd3) from ''Bifidobacterium adolescentis'' will remove an &alpha;-1,3-linked arabinofuranose from xylans where the xylose residue is substituted at both &alpha;-1,2 and &alpha;-1,3  with arabinose <cite>vandenBroek2005</cite>. By contrast some arabinofuranosidases are [[exo]]-&alpha;-1,5-L-arabinanases <cite>Matsuo2000</cite>. It should be noted that in several plant cell wall degrading organisms there has been a dramatic expansion in GH43 family enzymes, which may reflect a more extensive range of specificities than described to date.  In light of the sequence and functional diversity of GH43 members, this family has been divided into subfamilies <cite>Mewis2016</cite>.
 == Kinetics and Mechanism ==
@@ Line 59: / Line 59: @@
 #Brux2006 pmid=16631196
 #KerstersHilderson1976 pmid=1268883
 #Jiang2012 pmid=22960181
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH043]]

@@ Line 29: / Line 29: @@
 == Kinetics and Mechanism ==
-NMR, deploying arabinan as the substrate, showed that an [[endo]]-&alpha;-1,5-arabinanase uses an [[inverting]] mechanism <cite>Pitson1996</cite>. However, the first demonstration of an inverting enzyme, which was later shown to be a GH43 &beta;-xylosidase, was by using a linked assay with a anomeric stereospecific D-xylose isomerase <cite>KerstersHilderson1976</cite>.
+NMR, deploying arabinan as the substrate, showed that an [[endo]]-&alpha;-1,5-arabinanase uses an [[inverting]] mechanism <cite>Pitson1996</cite>. However, the first demonstration of an inverting enzyme, which was later shown to be a GH43 &beta;-xylosidase, was by using a linked assay with an anomeric stereospecific D-xylose isomerase <cite>KerstersHilderson1976</cite>.
 == Catalytic Residues ==

@@ Line 32: / Line 32: @@
 == Catalytic Residues ==
-The catalytic [[general base]], an aspartate, the catalytic [[general acid]], a glutamate, and an aspartate that modules the p''K''<sub>a</sub> of the general acid were identified through the crystal structure of ''Cellvibrio japonicus'' CjAbn43A, and confirmed by site-directed mutagenesis <cite>Nurizzo2002</cite>. Further biochemical proof for the catalytic function of the equivalent residues in a &beta;-xylosidase were obtained by demonstrating a relationship between the activity of the catalytic acid and the p''K''<sub>a</sub> of the leaving group of the substrate. The identity of the catalytic base was achieved by azide rescue of a mutant of this residue <cite>Shallom2005</cite>. In contrast to many [[inverting]] [[glycoside hydrolases]] there appears to be a single candidate catalytic general base for the arabinofuranosidases and xylosidases in this family, but this residue is absent in GH43 galactosidase <cite>REFMISSING</cite>.
+The catalytic [[general base]], an aspartate, the catalytic [[general acid]], a glutamate, and an aspartate that modules the p''K''<sub>a</sub> of the general acid were identified through the crystal structure of ''Cellvibrio japonicus'' CjAbn43A, and confirmed by site-directed mutagenesis <cite>Nurizzo2002</cite>. Further biochemical proof for the catalytic function of the equivalent residues in a &beta;-xylosidase were obtained by demonstrating a relationship between the activity of the catalytic acid and the p''K''<sub>a</sub> of the leaving group of the substrate. The identity of the catalytic base was achieved by azide rescue of a mutant of this residue <cite>Shallom2005</cite>. In contrast to many [[inverting]] [[glycoside hydrolases]] there appears to be a single candidate catalytic general base for the arabinofuranosidases and xylosidases in this family, but this residue is absent in GH43 galactosidase <cite>Jiang2012</cite>.
 == Three-dimensional structures ==
@@ Line 59: / Line 59: @@
 #Brux2006 pmid=16631196
 #KerstersHilderson1976 pmid=1268883
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH043]]

@@ Line 26: / Line 26: @@
 == Substrate specificities ==
-The major activities reported for this family of [[glycoside hydrolases]] are &alpha;-L-arabinofuranosidases <cite>#1</cite>, [[endo]]-&alpha;-L-arabinanases (or endo-processive arabinanases) <cite>#2#3</cite> and &beta;-D-xylosidases <cite>#4</cite> (for further details see: [[Absolute configuration: D/L nomenclature]]). An enzyme with [[exo]] &alpha;-1,3-galactanase has also been described <cite>#5</cite>. A significant number of enzymes in this family display both &alpha;-L-arabinofuranosidase and &beta;-D-xylosidase activity using aryl-glycosides as substrates. It is likely that the natural activity of these enzymes is conferred by the aglycone component of the substrate. Indeed, the arabionofuranosidase activities already reported target very different glycans. Thus, the ''Bacillus subtilis'' enzyme arabinoxylan &alpha;-L-arabinofuranohydrolase specifically removes arabinofuranose side chains that are linked either &alpha;-1,2 or &alpha;-1,3  to backbone xylose residues <cite>#6</cite>, while the arabinoxylan arabinofuranohydrolase-D3 (AXHd3) from ''Bifidobacterium adolescentis'' will remove an &alpha;-1,3-linked arabinofuranose from xylans where the xylose residue is substituted at both &alpha;-1,2 and &alpha;-1,3  with arabinose <cite>#7</cite>. By contrast some arabinofuranosidases are [[exo]]-&alpha;-1,5-L-arabinanases <cite>#8</cite>. It should be noted that in several plant cell wall degrading organisms there has been a dramatic expansion in GH43 family enzymes, which may reflect a more extensive range of specificities than described to date.
+The major activities reported for this family of [[glycoside hydrolases]] are &alpha;-L-arabinofuranosidases <cite>Flipphi1993a</cite>, [[endo]]-&alpha;-L-arabinanases (or endo-processive arabinanases) <cite>McKie1997 Flipphi1993b</cite> and &beta;-D-xylosidases <cite>Shallom2005</cite> (for further details see: [[Absolute configuration: D/L nomenclature]]). An enzyme with [[exo]] &alpha;-1,3-galactanase has also been described <cite>Ichinose2005</cite>. A significant number of enzymes in this family display both &alpha;-L-arabinofuranosidase and &beta;-D-xylosidase activity using aryl-glycosides as substrates. It is likely that the natural activity of these enzymes is conferred by the leaving-group component of the substrate. Indeed, the arabionofuranosidase activities already reported target very different glycans. Thus, the ''Bacillus subtilis'' enzyme arabinoxylan &alpha;-L-arabinofuranohydrolase specifically removes arabinofuranose side chains that are linked either &alpha;-1,2 or &alpha;-1,3  to backbone xylose residues <cite>Bourgois2007</cite>, while the arabinoxylan arabinofuranohydrolase-D3 (AXHd3) from ''Bifidobacterium adolescentis'' will remove an &alpha;-1,3-linked arabinofuranose from xylans where the xylose residue is substituted at both &alpha;-1,2 and &alpha;-1,3  with arabinose <cite>vandenBroek2005</cite>. By contrast some arabinofuranosidases are [[exo]]-&alpha;-1,5-L-arabinanases <cite>Matsuo2000</cite>. It should be noted that in several plant cell wall degrading organisms there has been a dramatic expansion in GH43 family enzymes, which may reflect a more extensive range of specificities than described to date.
 == Kinetics and Mechanism ==
-NMR, deploying arabinan as the substrate, showed that an [[endo]]-&alpha;-1,5-arabinanase uses an [[inverting]] mechanism <cite>#9</cite>. However, the first demonstration of an inverting enzyme, which was later shown to be a GH43 &beta;-xylosidase, was by using a linked assay with a anomeric stereospecific D-xylose isomerase <cite>#14</cite>.
+NMR, deploying arabinan as the substrate, showed that an [[endo]]-&alpha;-1,5-arabinanase uses an [[inverting]] mechanism <cite>Pitson1996</cite>. However, the first demonstration of an inverting enzyme, which was later shown to be a GH43 &beta;-xylosidase, was by using a linked assay with a anomeric stereospecific D-xylose isomerase <cite>KerstersHilderson1976</cite>.
 == Catalytic Residues ==
-The catalytic [[general base]], an aspartate, the catalytic [[general acid]], a glutamate, and an aspartate that modules the p''K''<sub>a</sub> of the general acid were identified through the crystal structure of ''Cellvibrio japonicus'' CjAbn43A, and confirmed by site-directed mutagenesis <cite>#10</cite>. Further biochemical proof for the catalytic function of the equivalent residues in a &beta;-xylosidase were obtained by demonstrating a relationship between the activity of the catalytic acid and the p''K''<sub>a</sub> of the leaving group of the substrate. The identity of the catalytic base was achieved by azide rescue of a mutant of this residue <cite>#4</cite>. In contrast to many [[inverting]] [[glycoside hydrolases]] there appears to be a single candidate catalytic general base for the arabinofuranosidases and xylosidases in this family, but this residue is absent in GH43 galactosidase <cite>#15</cite>.
+The catalytic [[general base]], an aspartate, the catalytic [[general acid]], a glutamate, and an aspartate that modules the p''K''<sub>a</sub> of the general acid were identified through the crystal structure of ''Cellvibrio japonicus'' CjAbn43A, and confirmed by site-directed mutagenesis <cite>Nurizzo2002</cite>. Further biochemical proof for the catalytic function of the equivalent residues in a &beta;-xylosidase were obtained by demonstrating a relationship between the activity of the catalytic acid and the p''K''<sub>a</sub> of the leaving group of the substrate. The identity of the catalytic base was achieved by azide rescue of a mutant of this residue <cite>Shallom2005</cite>. In contrast to many [[inverting]] [[glycoside hydrolases]] there appears to be a single candidate catalytic general base for the arabinofuranosidases and xylosidases in this family, but this residue is absent in GH43 galactosidase <cite>REFMISSING</cite>.
 == Three-dimensional structures ==
-The GH43 enzymes display a 'non-velcroed' five-bladed-&beta;-propeller. The propeller is based upon a five-fold repeat of blades composed of four-stranded &beta;-sheets <cite>#10</cite>.  The substrate-binding surface of Arb43A is in a long surface depression, with the catalytic constellation of carboxylates at its center. The exo-processive activity of the enzyme is conferred by a subtle steric block at the +3 subsite explaining why the enzyme releases, exclusively, arabinotriose <cite>#11</cite>. In the arabinofuranosidases and xylosidases the active site comprises a deep pocket and the orientation of the substrate is very different between the enzymes, which contributes to the varied specificities observed across the GH43 landscape <cite>#12#13</cite>.
+The GH43 enzymes display a 'non-velcroed' five-bladed-&beta;-propeller. The propeller is based upon a five-fold repeat of blades composed of four-stranded &beta;-sheets <cite>Nurizzo2002</cite>.  The substrate-binding surface of Arb43A is in a long surface depression, with the catalytic constellation of carboxylates at its center. The exo-processive activity of the enzyme is conferred by a subtle steric block at the +3 subsite explaining why the enzyme releases, exclusively, arabinotriose <cite>Proctor2005</cite>. In the arabinofuranosidases and xylosidases the active site comprises a deep pocket and the orientation of the substrate is very different between the enzymes, which contributes to the varied specificities observed across the GH43 landscape <cite>Vandermarliere2009 Brux2006</cite>.
 == Family Firsts ==
-;First sterochemistry determination: Determined for the ''Bacillus pumilus'' &beta;-xylosidase using an anomeric specific D-xylose isomerase <cite>14</cite> and determined for an arabinanase by proton NMR <cite>9</cite>.
+;First sterochemistry determination: Determined for the ''Bacillus pumilus'' &beta;-xylosidase using an anomeric specific D-xylose isomerase <cite>14</cite> and determined for an arabinanase by proton NMR <cite>Pitson1996</cite>.
-;First general base residue identification: Based on mutagensis informed by 3D structural data <cite>10</cite>
+;First general base residue identification: Based on mutagensis informed by 3D structural data <cite>Nurizzo2002</cite>
-;First general acid residue identification: Based on mutagensis informed by 3D structural data <cite>10</cite>
+;First general acid residue identification: Based on mutagensis informed by 3D structural data <cite>Nurizzo2002</cite>
-;First 3-D structure: &alpha;-L-arabinanase from ''Cellvibrio japonicus'' <cite>10</cite>.
+;First 3-D structure: &alpha;-L-arabinanase from ''Cellvibrio japonicus'' <cite>Nurizzo2002</cite>.
 == References ==
 <biblio>
-#1 pmid=7764056
+#Flipphi1993a pmid=7764056
-#2 pmid=9163351
+#McKie1997 pmid=9163351
-#3 pmid=7764386
+#Flipphi1993b pmid=7764386
-#4 pmid=15628881
+#Shallom2005 pmid=15628881
-#5 pmid=15866877
+#Ichinose2005 pmid=15866877
-#6 pmid=17426966
+#Bourgois2007 pmid=17426966
-#7 pmid=15650848
+#vandenBroek2005 pmid=15650848
-#8 pmid=10657233
+#Matsuo2000 pmid=10657233
-#9 pmid=8946944
+#Pitson1996 pmid=8946944
-#10 pmid=12198486
+#Nurizzo2002 pmid=12198486
-#11 pmid=15708971
+#Proctor2005 pmid=15708971
-#12 pmid=18980579
+#Vandermarliere2009 pmid=18980579
-#13 pmid=16631196
+#Brux2006 pmid=16631196
-#14 pmid=1268883
+#KerstersHilderson1976 pmid=1268883
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH043]]

@@ Line 32: / Line 32: @@
 == Catalytic Residues ==
-The catalytic [[general base]], an aspartate, the catalytic [[general acid]], a glutamate, and an aspartate that modules the p''K''<sub>a</sub> of the general acid were identified through the crystal structure of ''Cellvibrio japonicus'' CjAbn43A, and confirmed by site-directed mutagenesis <cite>#10</cite>. Further biochemical proof for the catalytic function of the equivalent residues in a &beta;-xylosidase were obtained by demonstrating a relationship between the activity of the catalytic acid and the p''K''<sub>a</sub> of the leaving group of the substrate. The identity of the catalytic base was achieved by azide rescue of a mutant of this residue <cite>#4</cite>. In contrast to many [[inverting]] [[glycoside hydrolases]] there appears to be a single candidate catalytic general base for the arabinofuranosidases and xylosidases in this family, but this residue is absent in GH43 galactosidase <cite>#11</cite>.
+The catalytic [[general base]], an aspartate, the catalytic [[general acid]], a glutamate, and an aspartate that modules the p''K''<sub>a</sub> of the general acid were identified through the crystal structure of ''Cellvibrio japonicus'' CjAbn43A, and confirmed by site-directed mutagenesis <cite>#10</cite>. Further biochemical proof for the catalytic function of the equivalent residues in a &beta;-xylosidase were obtained by demonstrating a relationship between the activity of the catalytic acid and the p''K''<sub>a</sub> of the leaving group of the substrate. The identity of the catalytic base was achieved by azide rescue of a mutant of this residue <cite>#4</cite>. In contrast to many [[inverting]] [[glycoside hydrolases]] there appears to be a single candidate catalytic general base for the arabinofuranosidases and xylosidases in this family, but this residue is absent in GH43 galactosidase <cite>#15</cite>.
 == Three-dimensional structures ==

@@ Line 21: / Line 21: @@
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
 |-
-| colspan="2" |http://www.cazy.org/fam/GH43.html
+| colspan="2" |{{CAZyDBlink}}GH43.html
 |}
 </div>

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