Glycoside Hydrolase Family 99

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

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Glycoside Hydrolase Family GH99
Clan	not assigned
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

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Catalytic Residues

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Three-dimensional structures

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Sample structures

Three-dimensional structure of GH99 endo-α-mannosidase from Bacteroides xylanisolvens, PDB code [1] [7].	Three-dimensional structure of GH99 endo-α-mannosidase from Bacteroides xylanisolvens bound to glucose-1,3-isofagomine and α-1,2- mannobiose, PDB code [2] [8].
<jmol> <jmolApplet> <color>white</color> <frame>true</frame> <uploadedFileContents>4ad1.pdb</uploadedFileContents> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select ligand; wireframe 0.3; select MG; spacefill; set spin Y 10; spin off; set antialiasDisplay OFF</script> </jmolApplet> </jmol>	<jmol> <jmolApplet> <color>white</color> <frame>true</frame> <uploadedFileContents>4ad4.pdb</uploadedFileContents> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select ligand; wireframe 0.3; select MG; spacefill; set spin Y 10; spin off; set antialiasDisplay OFF</script> </jmolApplet> </jmol>

Family Firsts

First stereochemistry determination

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First catalytic nucleophile identification

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First general acid/base residue identification

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First 3-D structure

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References

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