Glycosyltransferase Family 108 - Revision history

Harry Brumer at 18:31, 25 January 2026

2026-01-25T18:31:32Z

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

2021-12-18T21:16:41Z

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

Spencer Williams at 10:36, 19 September 2019

2019-09-19T10:36:13Z

Spencer Williams at 10:35, 19 September 2019

2019-09-19T10:35:37Z

Spencer Williams at 10:35, 19 September 2019

2019-09-19T10:35:17Z

Harry Brumer: added GH130 link

2019-09-18T17:42:13Z

added GH130 link

Spencer Williams at 12:59, 18 September 2019

2019-09-18T12:59:06Z

Spencer Williams at 12:58, 18 September 2019

2019-09-18T12:58:21Z

Spencer Williams at 12:57, 18 September 2019

2019-09-18T12:57:00Z

Spencer Williams at 12:55, 18 September 2019

2019-09-18T12:55:52Z

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 |-
 |'''Reactions'''
-|GDP-Man β-1,2-mannosyltransferase 2.4.1-, donor is GDP-α-Man; 1,2-β-oligomannan phosphorylase [{{EClink}}2.4.1.340 2.4.1.340], product is α-mannose-1-phosphate
+|GDP-Man β-1,2-mannosyltransferase 2.4.1-, donor is GDP-α-Man;<br>1,2-β-oligomannan phosphorylase [{{EClink}}2.4.1.340 2.4.1.340], product is α-mannose-1-phosphate
 |-
 |'''Active site residues'''

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Spencer Williams^^^
+* [[Author]]: [[User:Spencer Williams|Spencer Williams]]
-* [[Responsible Curator]]:  ^^^Spencer Williams^^^
+* [[Responsible Curator]]:  [[User:Spencer Williams|Spencer Williams]]
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 == Three-dimensional structures ==
-The three-dimensional structures of several GT108 proteins have been reported. The Structural Genomics of Pathogenic Protozoa Consortium (SGPP) deposited the first structure of a member of this family as a 'hypothetical protein' from ''L. major'' <cite>Holmes2005</cite>; the function of this protein remains unknown. The structures of several MPTs from ''L. mexicana'' have been reported <cite>Sernee2019</cite>. All proteins have a five-bladed β-propeller fold. Similar folds are predicted for other family members <cite>Sernee2019</cite>. A complex of the D94N variant of ''L. mexicana'' MPT2 with mannobiose highlighted this conserved residue as the likely [[general acid]] for the reverse phosphorolytic reaction. Superposition of the structures of the MPTs with GH130 β-mannoside phosphorylases highlighted conserved active site residues in the -1 subsite, and conserved interactions with the sugar residue. The Arg/His residues that correlates with GDP-Man transferase/mannoside phosphorylase activity were located in the active site cleft, in a position that was proposed to result in specific interactions with GDP or phosphate in the respective catalytic reactions <cite>Sernee2019</cite>.
+The three-dimensional structures of several GT108 proteins have been reported. The Structural Genomics of Pathogenic Protozoa Consortium (SGPP) deposited the first structure of a member of this family as a 'hypothetical protein' from ''L. major'' <cite>Holmes2005</cite>; the function of this protein remains unknown. The structures of several MPTs from ''L. mexicana'' have been reported <cite>Sernee2019</cite>. All proteins have a five-bladed β-propeller fold. Similar folds are predicted for other family members <cite>Sernee2019</cite>. A complex of the D94N variant of ''L. mexicana'' MPT2 with mannobiose highlighted this conserved residue as the likely [[general acid]] for the reverse phosphorolytic reaction. Superposition of the structures of the MPTs with [[GH130]] β-mannoside phosphorylases highlighted conserved active site residues in the -1 subsite, and conserved interactions with the sugar residue. The Arg/His residues that correlates with GDP-Man transferase/mannoside phosphorylase activity were located in the active site cleft, in a position that was proposed to result in specific interactions with GDP or phosphate in the respective catalytic reactions <cite>Sernee2019</cite>.
 == Family Firsts ==

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 |-
 |'''Clan'''
-GH-S
+|GH-S
 |-
 |'''Mechanism'''

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 |-
 |'''Clan'''
-|With [[GH130]], the first GH/GT clan
+GH-S
 |-
 |'''Mechanism'''

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 == Catalytic Residues ==
-Asp83 is the catalytic general base in the ''Leishmania mexicana'' MPT4 <cite>Sernee2019</cite>. The GDP-Man transferases MTP1 and MTP2 contain a His residue (His168 in MTP1 and His161 in MTP2) in the active site; at the equivalent position the phosphorolytic MTPs such as MTP4 contain an Arg residue (Arg150) <cite>Sernee2019</cite>.
+Asp83 is the catalytic general base in the ''Leishmania mexicana'' MPT4 <cite>Sernee2019</cite>. Activity as a mannosyltransferase or phosphorylase is achieved by a His/Arg switch: the GDP-Man transferases MTP1 and MTP2 contain a His residue (His168 in MTP1 and His161 in MTP2) in the active site; at the equivalent position the phosphorolytic MTPs such as MTP4 contain an Arg residue (Arg150) <cite>Sernee2019</cite>.
 == Three-dimensional structures ==

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 == Kinetics and Mechanism ==
-In the glycoside cleavage reaction this residue acts as a [[general acid]], protonating the glycosidic leaving group via a proton relay through the -1 subsite mannose 3-OH, allowing phosphate to displace the anomeric glycoside leaving group. In the reverse reaction involving mannosyl transfer from Man-1-P (or GDP-Man for MPT1 and 2), this residue acts as a [[general base]], deprotonating the 2-OH of the sugar nucleophile to promote glycosidic bond formation. The proposed mechanism is similar to that for family [[GH130]] β-1,2-mannoside phosphorylases <cite> Nakae2013</cite>
+In the glycoside cleavage reaction Asp83 of ''Leishmania mexicana'' MPT4 acts as a [[general acid]], protonating the glycosidic leaving group via a proton relay through the -1 subsite mannose 3-OH, allowing phosphate to displace the anomeric glycoside leaving group. In the reverse reaction involving mannosyl transfer from Man-1-P (or GDP-Man for MPT1 and 2), this residue acts as a [[general base]], deprotonating the 2-OH of the sugar nucleophile to promote glycosidic bond formation. The proposed mechanism is similar to that for family [[GH130]] β-1,2-mannoside phosphorylases <cite> Nakae2013</cite>
 == Catalytic Residues ==

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 == Substrate specificities ==
-The [[glycosyltransferases]] in family GT108 were originally identified by bioinformatics analysis using GH130 sequences as a query. This identified a tandem repeat of seven genes on chromosome 10 of ''Leishmania mexicana'' and varying numbers of orthologs in other trypanosomatids <cite>Sernee2019</cite>. A null mutant lacking the entire array of seven genes lost the ability to synthesize 1,2-β-oligomannan (termed mannogen). These enzymes were termed mannosyltransferase/phosphorylases (MTPs) owing to ability to both synthesize mannogen from GDPMan and/or Man-1-P, as well as an ability to catalyze phosphorolysis of mannogen to form Man-1-P. Specifically, the ''L. mexicana'' enzymes MPT3, MPT4, MPT6 and MPT7 catalyzed the phosphorolysis of mannogen to give Man-1-P, as well as the reverse reaction to synthesize mannogen by mannosyltransfer from Man-1-P. The ‘’L. Mexicana’’ enzymes MPT1 and MPT2 act as GDP-Man dependent β-1,2-mannosyltransferases, elongating mannogen, and lack detectable phosphorolytic activity.
+The [[glycosyltransferases]] in family GT108 were originally identified by bioinformatics analysis using GH130 sequences as a query. This identified a tandem repeat of seven genes on chromosome 10 of ''Leishmania mexicana'' and varying numbers of orthologs in other trypanosomatids <cite>Sernee2019</cite>. A null mutant lacking the entire array of seven genes lost the ability to synthesize 1,2-β-oligomannan (termed mannogen). These enzymes were termed mannosyltransferase/phosphorylases (MTPs) owing to ability to both synthesize mannogen from GDPMan and/or Man-1-P, as well as an ability to catalyze phosphorolysis of mannogen to form Man-1-P. Specifically, the ''L. mexicana'' enzymes MPT3, MPT4, MPT6 and MPT7 catalyze the phosphorolysis of mannogen to give Man-1-P, as well as the reverse reaction to synthesize mannogen by mannosyltransfer from Man-1-P. The ‘’L. mexicana’’ enzymes MPT1 and MPT2 act as GDP-Man dependent β-1,2-mannosyltransferases, elongating mannogen, and lack detectable phosphorolytic activity.
 == Kinetics and Mechanism ==