Glycosyltransferase Family 108

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• Author: ^^^Spencer Williams^^^
• Responsible Curator: ^^^Spencer Williams^^^

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Glycosyltransferase Family GT108
Clan	GT-x
inverting: GDP-Man β-1,2-mannosyltransferase (EC 2.4.99.-), donor is GDP-α-Man; 1,2-β-oligomannan phosphorylase (EC 2.4.1.340), product is α-mannose-1-phosphate
Active site residues	known
CAZy DB link
https://www.cazy.org/GT108.html

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 [1]. 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.

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 [2]

Catalytic Residues

Asp83 is the catalytic general base in the Leishmania mexicana MPT4. 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).

Three-dimensional structures

Content is to be added here.

Family Firsts

First catalytic residue identification

Asp83 in ‘’Leishmania mexicana’’ MPT4 and other MPT enzymes [1]. The His/Arg switch distinguishing GDP-Man dependent transferase activity, and phosphorolytic activity was also identified in this study.

First 3-D structure

The ‘’Leishmania major’’ strain Friedlin protein LMJF_10_1260 was determined by X-ray crystallography [3].

References

1. pmid= 31513773

2. Nakae S, Ito S, Higa M, Senoura T, Wasaki J, Hijikata A, Shionyu M, Ito S, and Shirai T. (2013). Structure of novel enzyme in mannan biodegradation process 4-O-β-D-mannosyl-D-glucose phosphorylase MGP. J Mol Biol. 2013;425(22):4468-78. DOI:10.1016/j.jmb.2013.08.002 |

3. 2B4W, Hypothetical protein from leishmania major [1].