CAZypedia - User contributions [en-ca]

Glycoside Hydrolase Family 38

2010-01-22T14:54:05Z

David Rose: /* References */

{{CuratorApproved}}
* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|none
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
[[Glycoside hydrolases]] of family 38 are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α-1,6 and α-1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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 α-mannosidase <cite>3</cite> and later confirmed by structural analysis of covalent [[intermediate]]s <cite>2</cite>

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The [[catalytic nucleophile]] of Asp204 (Golgi α-mannosidase II crystal structure numbering) was inferred from previous studies with Jack Bean α-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 ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-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: 1.2-1.6Å (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 α-mannosidase II was determined to 2.7Å 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 α/β portion and an all-β 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 [[general acid/base]] residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: Golgi α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462
#11 pmid=16115860
#12 pmid=19722277

</biblio>


[[Category:Glycoside Hydrolase Families|GH038]]

Glycoside Hydrolase Family 38

2010-01-22T14:51:51Z

David Rose: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|none
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
[[Glycoside hydrolases]] of family 38 are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α-1,6 and α-1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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 α-mannosidase <cite>3</cite> and later confirmed by structural analysis of covalent [[intermediate]]s <cite>2</cite>

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The [[catalytic nucleophile]] of Asp204 (Golgi α-mannosidase II crystal structure numbering) was inferred from previous studies with Jack Bean α-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 ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-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: 1.2-1.6Å (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 α-mannosidase II was determined to 2.7Å 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 α/β portion and an all-β 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 [[general acid/base]] residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: Golgi α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462
#11 pmid=16115860

</biblio>


[[Category:Glycoside Hydrolase Families|GH038]]

Glycoside Hydrolase Family 38

2009-08-21T21:19:48Z

David Rose:

* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
GH38 enzymes are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α1,6 and α1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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 operate by the conventional Koshland double-displacement retaining mechanism. This was initially determined by covalent intermediate trapping with the Jack Bean homologue <cite>3</cite> and later confirmed by structural analysis of covalent intermediates <cite>2</cite>

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The nucleophile Asp204 (Golgi α-mannosidase II crystal structure numbering) was inferred from previous studies with Jack Bean mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely acid-base catalyst.

== Three-dimensional structures ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and catalytic intermediate mimics. Many of these are at very high resolution: 1.2-1.6Å (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 α-mannosidase II was determined to 2.7Å 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 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 α/β portion and an all-β 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 general acid/base residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: Golgi α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462
#11 pmid=16115860

</biblio>


[[Category:Glycoside Hydrolase Families|GH038]]

Glycoside Hydrolase Family 38

2009-08-21T21:09:13Z

David Rose:

* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
GH38 enzymes are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α1,6 and α1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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 operate by the conventional Koshland double-displacement retaining mechanism. This was initially determined by covalent intermediate trapping with the Jack Bean homologue <cite>3</cite> and later confirmed by structural analysis of covalent intermediates <cite>5</cite>

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The nucleophile Asp204 (Golgi α-mannosidase II numbering) was inferred from previous studies with Jack Bean mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely acid-base catalyst.

== Three-dimensional structures ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and catalytic intermediate mimics. Many of these are at very high resolution: 1.2-1.6Å (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 α-mannosidase II was determined to 2.7Å resolution indicated interesting low-pH activation effects <cite>4</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 α/β portion and an all-β 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 general acid/base residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: Golgi α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462
#11 pmid=16115860

</biblio>


[[Category:Glycoside Hydrolase Families|GH038]]

Glycoside Hydrolase Family 38

2009-08-20T17:39:17Z

David Rose:

* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
GH38 enzymes are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α1,6 and α1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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</cite><cite>11</cite>.

== Kinetics and Mechanism ==
GH38 enzymes operate by the conventional Koshland double-displacement retaining mechanism.
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.

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The nucleophile Asp204 (Golgi α-mannosidase II numbering) was inferred from previous studies with Jack Bean mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely acid-base catalyst.

== Three-dimensional structures ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and catalytic intermediate mimics. Many of these are at very high resolution: 1.2-1.6Å (<cite>5</cite><cite>6</cite><cite>7</cite><cite>8</cite><cite>9</cite> for examples). An enzyme-substrate complex has also been determined <cite>10</cite>
The crystal structure of bovine lysosomal α-mannosidase II was determined to 2.7Å resolution indicated interesting low-pH activation effects <cite>4</cite> .

== Family Firsts ==
;First sterochemistry determination:
;First catalytic nucleophile identification: Jack Bean mannosidase <cite>3</cite>
;First general acid/base residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: Golgi α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462
#11 pmid=16115860

</biblio>


<nowiki>[[Category:Glycoside Hydrolase Families]]</nowiki>

Glycoside Hydrolase Family 38

2009-08-20T17:36:37Z

David Rose:

* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
GH38 enzymes are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α1,6 and α1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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</cite><cite>11</cite>.

== Kinetics and Mechanism ==
GH38 enzymes operate by the conventional Koshland double-displacement retaining mechanism.
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 play a role in protein recognition or signalling.

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The nucleophile Asp204 (Golgi α-mannosidase II numbering) was inferred from previous studies with Jack Bean mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely acid-base catalyst.

== Three-dimensional structures ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and catalytic intermediate mimics. Many of these are at very high resolution: 1.2-1.6Å (<cite>5</cite><cite>6</cite><cite>7</cite><cite>8</cite><cite>9</cite> for examples). An enzyme-substrate complex has also been determined <cite>10</cite>
The crystal structure of bovine lysosomal α-mannosidase II was determined to 2.7Å resolution indicated interesting low-pH activation effects <cite>4</cite> .

== Family Firsts ==
;First sterochemistry determination:
;First catalytic nucleophile identification: Jack Bean mannosidase <cite>3</cite>
;First general acid/base residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: Golgi α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462
#11 pmid=16115860

</biblio>


<nowiki>[[Category:Glycoside Hydrolase Families]]</nowiki>

Glycoside Hydrolase Family 38

2009-08-20T17:30:48Z

David Rose:

'''The text below is a template to help you create a consistent layout for GH entries. To get an idea of what to put in each field, save this edit and have a look at any of the GH families by following this link: [[:Category:Glycoside Hydrolase Families]]''' ''(TIP: Right click with your mouse and open the link in a new browser window...)''

Make sure to delete this text and the four dashes (line) below when you are done with your page!
----

* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
GH38 enzymes are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α1,6 and α1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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</cite><cite>11</cite>.

== Kinetics and Mechanism ==
GH38 enzymes operate by the conventional Koshland double-displacement retaining mechanism.
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 play a role in protein recognition or signalling.

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The nucleophile Asp204 (Golgi α-mannosidase II numbering) was inferred from previous studies with Jack Bean mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely acid-base catalyst.

== Three-dimensional structures ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and catalytic intermediate mimics. Many of these are at very high resolution: 1.2-1.6Å (<cite>5</cite><cite>6</cite><cite>7</cite><cite>8</cite><cite>9</cite> for examples). An enzyme-substrate complex has also been determined <cite>10</cite>
The crystal structure of bovine lysosomal α-mannosidase II was determined to 2.7Å resolution indicated interesting low-pH activation effects <cite>4</cite> .

== Family Firsts ==
;First sterochemistry determination:
;First catalytic nucleophile identification: Jack Bean mannosidase <cite>3</cite>
;First general acid/base residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: Golgi α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462
#11 pmid=16115860

</biblio>


<nowiki>[[Category:Glycoside Hydrolase Families]]</nowiki>

Glycoside Hydrolase Family 38

2009-08-20T17:18:49Z

David Rose:

'''The text below is a template to help you create a consistent layout for GH entries. To get an idea of what to put in each field, save this edit and have a look at any of the GH families by following this link: [[:Category:Glycoside Hydrolase Families]]''' ''(TIP: Right click with your mouse and open the link in a new browser window...)''

Make sure to delete this text and the four dashes (line) below when you are done with your page!
----

* [[Author]]: [[User:David Rose|David Rose]]
* [[Responsible Curator]]: [[User:David Rose|David Rose]]
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH38'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH38.html
|}
</div>

== Substrate specificities ==
GH38 enzymes are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α1,6 and α1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α1,6). GH38 active sites can be quite long and open, and some are sensitive to the polysaccharide substrate structure. For example, Golgi α-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</cite>.

== Kinetics and Mechanism ==
GH38 enzymes operate by the conventional Koshland double-displacement retaining mechanism.
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 play a role in protein recognition or signalling.

== Catalytic Residues ==
Both catalytic side chains are Asp residues. The nucleophile Asp204 (Golgi α-mannosidase II numbering) was inferred from previous studies with Jack Bean mannosidase <cite>3</cite> and confirmed in the crystal structures of covalent intermediates <cite>2</cite>. Mutagenesis studies implicated Asp341 as the likely acid-base catalyst.

== Three-dimensional structures ==
The crystal structure of the GH38 domain of ''Drosophila'' Golgi α-mannosidase II <cite>1</cite> has been determined in complex with a large number of inhibitors and catalytic intermediate mimics. Many of these re at very high resolution (<cite>5</cite><cite>6</cite><cite>7</cite><cite>8</cite><cite>9</cite> for examples). An enzyme-substrate complex has also been determined <cite>10</cite>
The crystal structure of bovine lysosomal α-mannosidase II was determined to 2.7A resolution indicated interesting low-pH activation effects <cite>4</cite> .

== Family Firsts ==
;First sterochemistry determination:
;First catalytic nucleophile identification: Jack Bean mannosidase <cite>3</cite>
;First general acid/base residue identification: Golgi α-mannosidase II covalent intermediate stabilization <cite>2</cite>
;First 3-D structure: α-mannosidase II <cite>1</cite>

== References ==
<biblio>
#1 pmid=11406577
#2 pmid=12960159
#3 pmid=9442045
#4 pmid=12634058
#5 pmid=14636047
#6 pmid=16787095
#7 pmid=18076078
#8 pmid=18558690
#9 pmid=18599296
#10 pmid=18599462

</biblio>


<nowiki>[[Category:Glycoside Hydrolase Families]]</nowiki>

Glycoside Hydrolase Family 38

2009-08-20T15:46:14Z

David Rose:

Glycoside Hydrolase Family 38

2009-08-20T15:34:03Z

David Rose:

User:David Rose

2009-06-26T12:26:54Z

David Rose:

== ''Biography'' ==

David is originally from Buffalo, New York and completed his undergraduate training in Biophysics at the University of Pennsylvania. He spent one of his undergraduate summers as a research assistant with Greg Petsko at Wayne State University (his family having relocated to the Detroit area) and the rest is history. From Penn, David pursued his D. Phil. at Oxford under Sir David Phillips, working on a collaborative project with Raymond Dwek, thus seeding his interest in carbohydrate-protein interactions. In 1981, he began a postdoc with Greg Petsko, then at MIT, working on antibody structures. In 1984, David immigrated permanently to Canada, as a Research Associate at the National Research Council in Ottawa, and began his work on glycoside hydrolases with a protein engineering project on a GH11 xylanase. On establishment of his own laboratory in 1991 at the Ontario Cancer Institute in Toronto, he continued his participation in the Protein Engineering Network of Centres of Excellence (PENCE), where he teamed up with Steve Withers, Lawrence McIntosh, Tony Warren and others in early studies on the GH10 Cex/CfXyn10A xylanase and its catalytic intermediates. In Toronto, David developed an interest in eukaryotic glycoside hydrolases and his group began a long-term structural, mutagenesis and inhibitor analysis of the GH38 Golgi α-mannosidase II, again in collaboration with Steve Withers and subsequently many other carbohydrate chemists, including Mario Pinto. More recently, David's group has been studying human intestinal glycosidases involve in nutritional starch digestion, the GH31 maltase-glucoamylase and sucrase-isomaltase. In January, 2009, David moved to become Chair of the Department of Biology at University of Waterloo.

More information about David's research can be found at his [http://www.biology.uwaterloo.ca/people/rose/index.html home page].

[[Category:Contributors|Rose, David]]

User:David Rose

2009-06-26T12:24:40Z

David Rose:

Biography:

David is originally from Buffalo, New York and completed his undergraduate training in Biophysics at the University of Pennsylvania. He spent one of his undergraduate summers as a research assistant with Greg Petsko at Wayne State University (his family having relocated to the Detroit area) and the rest is history. From Penn, David pursued his D. Phil. at Oxford under Sir David Phillips, working on a collaborative project with Raymond Dwek, thus seeding his interest in carbohydrate-protein interactions. In 1981, he began a postdoc with Greg Petsko, then at MIT, working on antibody structures. In 1984, David immigrated permanently to Canada, as a Research Associate at the National Research Council in Ottawa, and began his work on glycoside hydrolases with a protein engineering project on a GH11 xylanase. On establishment of his own laboratory in 1991 at the Ontario Cancer Institute in Toronto, he continued his participation in the Protein Engineering Network of Centres of Excellence (PENCE), where he teamed up with Steve Withers, Lawrence McIntosh, Tony Warren and others in early studies on the GH10 Cex/CfXyn10A xylanase and its catalytic intermediates. In Toronto, David developed an interest in eukaryotic glycoside hydrolases and his group began a long-term structural, mutagenesis and inhibitor analysis of the GH38 Golgi α-mannosidase II, again in collaboration with Steve Withers and subsequently many other carbohydrate chemists, including Mario Pinto. More recently, David's group has been studying human intestinal glycosidases involve in nutritional starch digestion, the GH31 maltase-glucoamylase and sucrase-isomaltase. In January, 2009, David moved to become Chair of the Department of Biology at University of Waterloo.

More information about David's research can be found at his [http://www.biology.uwaterloo.ca/people/rose/index.html home page].

[[Category:Contributors|Rose, David]]

User:David Rose

2009-06-26T12:17:28Z

David Rose:

David is originally from Buffalo, New York and completed his undergraduate training in Biophysics at the University of Pennsylvania. He spent one of his undergraduate summers as a research assistant with Greg Petsko at Wayne State University (his family having relocated to the Detroit area) and the rest is history. From Penn, David pursued his D. Phil. at Oxford under Sir David Phillips, working on a collaborative project with Raymond Dwek, thus seeding his interest in carbohydrate-protein interactions. In 1981, he began a postdoc with Greg Petsko, then at MIT, working on antibody structures. In 1984, David immigrated permanently to Canada, as a Research Associate at the National Research Council in Ottawa, and began his work on glycoside hydrolases with a protein engineering project on a GH11 xylanase. On establishment of his own laboratory in 1991 at the Ontario Cancer Institute in Toronto, he continued his participation in the Protein Engineering Network of Centres of Excellence (PENCE), where he teamed up with Steve Withers, Lawrence McIntosh, Tony Warren and others in early studies on the GH10 Cex/CfXyn10A xylanase and its catalytic intermediates. In Toronto, David developed an interest in eukaryotic glycoside hydrolases and his group began a long-term structural, mutagenesis and inhibitor analysis of the GH38 Golgi α-mannosidase II, again in collaboration with Steve Withers and subsequently many other carbohydrate chemists, including Mario Pinto. More recently, David's group has been studying human intestinal glycosidases involve in nutritional starch digestion, the GH31 maltase-glucoamylase and sucrase-isomaltase. In January, 2009, David moved to become Chair of the Department of Biology at University of Waterloo.

[[Category:Contributors|Rose, David]]

User:David Rose

2009-06-26T12:17:02Z

David Rose:

User talk:David Rose

2009-06-25T16:24:06Z

David Rose: Removing all content from page

User:David Rose

2009-06-25T16:23:32Z

David Rose: New page: David is originally from Buffalo, New York and completed his undergraduate training in Biophysics at the University of Pennsylvania. He spent one of his undergraduate summers as a research...

Glycoside Hydrolase Family 38

2009-06-25T16:21:12Z

David Rose: New page:  '''The text below is a template to help you create a consistent layout for GH entries. To get an idea of w...

User talk:David Rose

2009-06-25T15:18:24Z

David Rose:

User talk:David Rose

2009-06-25T15:09:42Z

David Rose:

David is originally from Buffalo, New York and completed his undergraduate training in Biophysics at the University of Pennsylvania. He spent one of his undergraduate summers as a research assistant with Greg Petsko at Wayne State University (his family having relocated to the Detroit area) and the rest is history. From Penn, David pursued his D. Phil. at Oxford under Sir David Phillips, working on a collaborative project with Raymond Dwek, thus seeding his interest in carbohydrate-protein interactions. In 1981, he began a postdoc with Greg Petsko, then at MIT, working on antibody structures. In 1984, David immigrated permanently to Canada, as a Research Associate at the National Research Council in Ottawa, and began his work on glycoside hydrolases with a protein engineering project on a GH11 xylanase. On establishment of his own laboratory in 1991 at the Ontario Cancer Institute in Toronto, he continued his participation in the Protein Engineering Network of Centres of Excellence (PENCE), where he teamed up with Steve Withers, Lawrence McIntosh, Tony Warren and others in early studies on the GH10 Cex/CfXyn10A xylanase and its catalytic intermediates. In Toronto, David developed an interest in eukaryotic glycoside hydrolases and his group began a long-term structural, mutagenesis and inhibitor analysis of the GH38 Golgi alpha-mannosidase II, again in collaboration with Steve Withers and subsequently many other carbohydrate chemists, including Mario Pinto. More recently, David's group has been studying human intestinal glycosidases involve in nutritional starch digestion, the GH31 maltase-glucoamylase and sucrase-isomaltase. In January, 2009, David moved to become Chair of the Department of Biology at University of Waterloo.

User talk:David Rose

2009-06-25T15:07:35Z

David is originally from Buffalo, New York and completed his undergraduate training in Biophysics at the University of Pennsylvania. He spent one of his undergraduate summers as a research assistant with Greg Petsko at Wayne State University (his family having relocated to the Detroit area) and the rest is history. From Penn, David pursued his D. Phil. at Oxford under Sir David Phillips, working on a collaborative project with Raymond Dwek, thus seeding his interest in carbohydrate-protein interactions. In 1981, he began a postdoc with Greg Petsko, then at MIT, working on antibody structures. In 1984, David immigrated permanently to Canada, as a Research Associate at the National Research Council in Ottawa, and began his work on glycoside hydrolases with a protein engineering project on a GH11 xylanase. On establishment of his own laboratory at the Ontario Cancer Institute in Toronto, he continued his participation in the Protein Engineering Network of Centres of Excellence (PENCE), where he teamed up with Steve Withers, Lawrence McIntosh, Tony Warren and others in early studies on the GH10 Cex/CfXyn10A xylanase and its catalytic intermediates. In Toronto, David developed an interest in eukaryotic glycoside hydrolases and his group began a long-term structural, mutagenesis and inhibitor analysis of the GH38 Golgi alpha-mannosidase II, again in collaboration with Steve Withers and subsequently many other carbohydrate chemists, including Mario Pinto. More recently, David's group has been studying human intestinal glycosidases involve in nutritional starch digestion, the GH31 maltase-glucoamylase and sucrase-isomaltase. In January, 2009, David moved to become Chair of the Department of Biology at University of Waterloo.