|Protein name||Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase||mannosyl-oligosaccharide 1,2-alpha-mannosidasemannosidase 1Amannosidase 1B1,2-alpha-mannosidaseexo-alpha-1,2-mannanasemannose-9 processing alpha-mannosidaseglycoprotein processing mannosidase Imannosidase IMan9-mannosidaseManI1,2-alpha-mannosyl-oligosaccharide alpha-D-mannohydrolase|
|Synonyms||EC 220.127.116.11ER alpha-1,2-mannosidaseMannosidase alpha class 1B member 1Man9GlcNAc2-specific-processing alpha-mannosidase|
NM_016219.4 (DNA/RNA sequence)
|CAZy||GH47 (Glycoside Hydrolase Family)|
|MAP00513||High-mannose type N-glycan biosynthesis|
|MAP01030||Glycan structures - biosynthesis 1|
|Activity||Hydrolysis of the terminal (1->2)-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide Man(9)(GlcNAc)(2).|
|Subcellular location||Endoplasmic reticulum membrane, Single-pass type II membrane protein.|
|pdb||Catalytic residues||Cofactor-binding residues||comment|
| || || || || || || || || || || |
|1fmiA||GLU 330;ASP 463;GLU 599||THR 688(Calcium binding)|| |
|1fo2A||GLU 330;ASP 463;GLU 599||THR 688(Calcium binding)||mutant deletion T241|
|1fo3A||GLU 330;ASP 463;GLU 599||THR 688(Calcium binding)||mutant deletion T241|
|1x9dA||GLU 330;ASP 463;GLU 599||THR 688(Calcium binding)|| |
|References for Catalytic Mechanism|
|References||Sections||No. of steps in catalysis|
|Authors||Tremblay LO, Herscovics A|
|Title||Cloning and expression of a specific human alpha 1,2-mannosidase that trims Man9GlcNAc2 to Man8GlcNAc2 isomer B during N-glycan biosynthesis.|
|Journal||Biosci Biotechnol Biochem|
|Title||Unique catalytic and molecular properties of hydrolases from Aspergillus used in Japanese bioindustries.|
|Journal||J Biol Chem|
|Authors||Vallee F, Karaveg K, Herscovics A, Moremen KW, Howell PL|
|Title||Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases.|
|Authors||Jordan IK, Bishop GR, Gonzalez DS|
|Title||Sequence and structural aspects of functional diversification in class I alpha-mannosidase evolution.|
|Authors||Mulakala C, Reilly PJ|
|Title||Understanding protein structure-function relationships in Family 47 alpha-1,2-mannosidases through computational docking of ligands.|
|This enzyme belongs to the glycosyl hydrolase family-47, with an inverting mechanism.|
Class I alpha-1,2-alpha-mannosidase (glycosylhydrolase family 47) includes 2 subgroups, Endoplasmic Reticulum subgroup and Golgi subgroup. This entry is for ER subgroup from yeast. Another ER subgroup enzyme from yeast is included in S00051 (EzCatDB).
This enzyme is composed of the N-terminal cytoplasmic domain, transmembrane region, and the C-terminal lumenal domain, which is the catalytic domain. It is bound to Endoplasmic reticulum. Only the structure of the C-terminal catalytic domain has been determined.
According to the literature , although the calcium ion is necessary for the catalytic reaction, it is not directly involved in catalysis, stabilizng the conformation of Man saccharide through its interactions with O2' and O3' hydroxyl groups. However, the paper  suggested that the calcium ion is directly bound to the nucleophilic water, and probably involved in catalysis, as well. Although the calcium ion rarely activates a water, it may stabilize its negative charge.
According to the literature ,  and the structure with substrate analogue (PDB;1x9d), the catalytic reaction may proceeds as follows:
(1) Glu599 acts as a general base, to activate a water molecule (HOH 5 in 1x9d). The water is also bound to the Ca2+.
(2) The activated water makes a nucleophilic attack on the C1 atom of Man10.
(3) Glu330 acts as a general acid, to protonate leaving O2 atom of Man7, through a water (HOH 8 in 1x9d).