Glycoside Hydrolase Family 99

This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.

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

---

Glycoside Hydrolase Family GH99
Clan	GH-x
Mechanism	retaining/inverting
Active site residues	known/not known
CAZy DB link
https://www.cazy.org/GH99.html

Substrate specificities

Glycoside hydrolases of family GH99 are endo-acting α-mannosidases that cleave glucose-substituted mannose within immature N-linked glycans of the general formula Glc_1-3Man₉GlcNAc₂, with maximal activity on the monoglucosylated forms [1]. This family was originally created from mammalian enzyme, cloned by Spiro and co-workers [2]. Mammalian GH99 enzymes are localized to the Golgi apparatus [3] and appear to play a role in the rescue of glucosylated N-linked glycans that have evaded the action of the endoplasmic reticulum exo-glucosidases I and II [4]. Mammalian endo-α-mannosidases has increased activity on glucosylated N-linked glycans that have been trimmed in the non-glucose-substituted branches [2]. There is evidence that mammalian endo-α-mannosidases act on dolichol-bound N-glycan precursors [5], as well as free oligosaccharides released from N-glycoproteins and which undergo retrograde transport through the secretory pathway [6].

Kinetics and Mechanism

Content is to be added here.

Catalytic Residues

Content is to be added here.

Three-dimensional structures

Content is to be added here.

Family Firsts

First stereochemistry determination

Content is to be added here.

First catalytic nucleophile identification

Content is to be added here.

First general acid/base residue identification

Content is to be added here.

First 3-D structure

Content is to be added here.

References

1. Roth J, Ziak M, and Zuber C. (2003). The role of glucosidase II and endomannosidase in glucose trimming of asparagine-linked oligosaccharides. Biochimie. 2003;85(3-4):287-94. DOI:10.1016/s0300-9084(03)00049-x |
2. Spiro MJ, Bhoyroo VD, and Spiro RG. (1997). Molecular cloning and expression of rat liver endo-alpha-mannosidase, an N-linked oligosaccharide processing enzyme. J Biol Chem. 1997;272(46):29356-63. DOI:10.1074/jbc.272.46.29356 |
3. Zuber C, Spiro MJ, Guhl B, Spiro RG, and Roth J. (2000). Golgi apparatus immunolocalization of endomannosidase suggests post-endoplasmic reticulum glucose trimming: implications for quality control. Mol Biol Cell. 2000;11(12):4227-40. DOI:10.1091/mbc.11.12.4227 |
4. Dale MP, Kopfler WP, Chait I, and Byers LD. (1986). Beta-glucosidase: substrate, solvent, and viscosity variation as probes of the rate-limiting steps. Biochemistry. 1986;25(9):2522-9. DOI:10.1021/bi00357a036 |
6. Kukushkin NV, Alonzi DS, Dwek RA, and Butters TD. (2011). Demonstration that endoplasmic reticulum-associated degradation of glycoproteins can occur downstream of processing by endomannosidase. Biochem J. 2011;438(1):133-42. DOI:10.1042/BJ20110186 |