Glycoside Hydrolase Family 38 - Revision history

Harry Brumer: updated CAZyDBlink

2012-09-10T16:36:22Z

updated CAZyDBlink

Spencer Williams at 11:00, 22 June 2010

2010-06-22T11:00:55Z

Spencer Williams at 08:43, 2 February 2010

2010-02-02T08:43:56Z

David Rose: /* References */

2010-01-22T14:54:05Z

References

David Rose: /* Three-dimensional structures */

2010-01-22T14:51:51Z

Three-dimensional structures

Harry Brumer at 16:35, 13 January 2010

2010-01-13T16:35:15Z

Harry Brumer at 14:03, 8 November 2009

2009-11-08T14:03:45Z

Spencer Williams: /* Kinetics and Mechanism */

2009-09-01T04:32:49Z

Kinetics and Mechanism

Spencer Williams at 04:28, 1 September 2009

2009-09-01T04:28:57Z

Spencer Williams at 01:48, 1 September 2009

2009-09-01T01:48:13Z

@@ Line 20: / Line 20: @@
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
 |-
-| colspan="2" |http://www.cazy.org/fam/GH38.html
+| colspan="2" |{{CAZyDBlink}}GH38.html
 |}
 </div>

@@ Line 33: / Line 33: @@
 == Catalytic Residues ==
-Both catalytic side chains are Asp residues. The [[catalytic nucleophile]] of Asp204 (Golgi &alpha;-mannosidase II crystal structure numbering) was inferred from previous studies with Jack Bean &alpha;-mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely [[catalytic acid/base]] residue.
+Both catalytic side chains are Asp residues. The [[catalytic nucleophile]] of Asp204 (Golgi &alpha;-mannosidase II crystal structure numbering) was inferred from previous studies with jack Bean &alpha;-mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely [[catalytic acid/base]] residue.
 == Three-dimensional structures ==

@@ Line 25: / Line 25: @@
 == Substrate specificities ==
-[[Glycoside hydrolases]] of family 38 are Class II &alpha;-mannosidases. They range in breadth of specificity from the Golgi &alpha;-mannosidase (2A1), which has a dual specificity for &alpha;-1,6 and &alpha;-1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves &alpha;1,2, &alpha;1,3 and &alpha;1,6 linkages) or narrow specificities (2B2 is specific for &alpha;1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi &alpha;-mannosidase II requires the presence of a GlcNAc residue some five residues away from the cleavage site, while lysosomal mannosidases do not have that requirement <cite>1 11</cite>.
+[[Glycoside hydrolases]] of family 38 are Class II &alpha;-mannosidases. They range in breadth of specificity from the Golgi &alpha;-mannosidase (2A1), which has a dual specificity for &alpha;-1,6 and &alpha;-1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves &alpha;1,2, &alpha;1,3 and &alpha;1,6 linkages) or narrow specificities (2B2 is specific for &alpha;-1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi &alpha;-mannosidase II requires the presence of a GlcNAc residue some five residues away from the cleavage site, while lysosomal mannosidases do not have that requirement <cite>1 11</cite>.
 There have been GH38 mannosidases identified in a number of different localizations, classed into subfamilies with different substrate specificities and biochemical properties, and, presumably, different physiological roles. The Golgi enzyme is identified as 2A1 (Class 2, A for Golgi, enzyme 1). Lysosomal GH38 mannosidases are indicated by 'B' (2B1, 2B2) and those likely existing in the cytoplasm by 'C'.
 Physiological roles have been identified for the Golgi enzyme in the protein N-glycosylation pathway and lysosomal mannosidases in general are likely to be involved in scavenging of degraded glycoproteins. Roles for the cytoplasmic subclass have not been identified definitively, but they may play a role in protein recognition or signalling.
 == Kinetics and Mechanism ==
-GH38 enzymes are anomeric-configuration [[retaining]] enzymes that operate by the classical [[Koshland double-displacement mechanism]]. This was initially determined by trapping of the covalent [[intermediate]] with Jack Bean &alpha;-mannosidase <cite>3</cite> and later confirmed by structural analysis of covalent [[intermediate]]s <cite>2</cite>
+GH38 enzymes are anomeric-configuration [[retaining]] enzymes that operate by the classical [[Koshland double-displacement mechanism]]. This was initially determined by trapping of the covalent [[intermediate]] with jack bean &alpha;-mannosidase <cite>3</cite> and later confirmed by structural analysis of covalent [[intermediate]]s <cite>2</cite>
 == Catalytic Residues ==
@@ Line 37: / Line 37: @@
 == Three-dimensional structures ==
 The crystal structure of the GH38 domain of ''Drosophila'' Golgi &alpha;-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and [[intermediate]] mimics. Many of these are at very high resolution: 1.2-1.6&Aring; (see <cite>5 6 7 8 9</cite> for examples). An enzyme-substrate complex has also been determined <cite>10</cite>.
-The crystal structure of bovine lysosomal &alpha;-mannosidase II was determined to 2.7&Aring; resolution indicated interesting low-pH activation effects <cite>4</cite>. Some of the lysosomal enzymes show a metal dependency for activity.  Mutations in the residues proposed to be involved with metal binding are associated with lysosomal storage diseases <cite>12</cite>.
+The crystal structure of bovine lysosomal &alpha;-mannosidase II was determined to 2.7&Aring; resolution and displayedinteresting low-pH activation effects <cite>4</cite>. Some of the lysosomal enzymes show a metal dependency for activity.  Mutations in the residues proposed to be involved with metal binding are associated with lysosomal storage diseases <cite>12</cite>.
 The GH38 fold has been referred to as the "mannosidase fold". It is one large (approximately 1000-residue) globular domain, which can be roughly divided by secondary structure into an &alpha;/&beta; portion and an all-&beta; region. The former portion contains the active site, anchored by a Zn atom, which forms an integral part of the -1 site, interacting with the saccharide and helping to induce substrate distortion <cite>1</cite>.
 == Family Firsts ==
 ;First sterochemistry determination:
-;First [[catalytic nucleophile]] identification: Jack Bean mannosidase <cite>3</cite>
+;First [[catalytic nucleophile]] identification: Jack bean mannosidase <cite>3</cite>
 ;First [[general acid/base]] residue identification: Golgi &alpha;-mannosidase II covalent intermediate stabilization <cite>2</cite>
 ;First 3-D structure: Golgi &alpha;-mannosidase II <cite>1</cite>

@@ Line 59: / Line 59: @@
 #10 pmid=18599462
 #11 pmid=16115860
 </biblio>

@@ Line 37: / Line 37: @@
 == Three-dimensional structures ==
 The crystal structure of the GH38 domain of ''Drosophila'' Golgi &alpha;-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and [[intermediate]] mimics. Many of these are at very high resolution: 1.2-1.6&Aring; (see <cite>5 6 7 8 9</cite> for examples). An enzyme-substrate complex has also been determined <cite>10</cite>.
-The crystal structure of bovine lysosomal &alpha;-mannosidase II was determined to 2.7&Aring; resolution indicated interesting low-pH activation effects <cite>4</cite>. Some of the lysosomal enzymes show a metal dependency for activity.  Mutations in the residues proposed to be involved with metal binding are associated with lysosomal storage diseases (Venkatesan, Kuntz & Rose in press).
+The crystal structure of bovine lysosomal &alpha;-mannosidase II was determined to 2.7&Aring; resolution indicated interesting low-pH activation effects <cite>4</cite>. Some of the lysosomal enzymes show a metal dependency for activity.  Mutations in the residues proposed to be involved with metal binding are associated with lysosomal storage diseases <cite>12</cite>.
 The GH38 fold has been referred to as the "mannosidase fold". It is one large (approximately 1000-residue) globular domain, which can be roughly divided by secondary structure into an &alpha;/&beta; portion and an all-&beta; region. The former portion contains the active site, anchored by a Zn atom, which forms an integral part of the -1 site, interacting with the saccharide and helping to induce substrate distortion <cite>1</cite>.

@@ Line 10: / Line 10: @@
 |-
 |'''Clan'''
-|GH-x
+|none
 |-
 |'''Mechanism'''

← Older revision		Revision as of 14:03, 8 November 2009
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		+	{{CuratorApproved}}
	* [[Author]]: [[User:David Rose\|David Rose]]		* [[Author]]: [[User:David Rose\|David Rose]]
	* [[Responsible Curator]]: [[User:David Rose\|David Rose]]		* [[Responsible Curator]]: [[User:David Rose\|David Rose]]