DB code: D00470

RLCP classification 1.30.11370.560 : Hydrolysis
CATH domain -.-.-.- :
1.50.10.50 : Glycosyltransferase Catalytic domain
E.C. 3.2.1.113
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.50.10.50 : Glycosyltransferase S00051

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq CAZy Pfam
Q9UKM7 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase
EC 3.2.1.113
ER alpha-1,2-mannosidase
Mannosidase alpha class 1B member 1
Man9GlcNAc2-specific-processing alpha-mannosidase
NP_057303.2 (Protein)
NM_016219.4 (DNA/RNA sequence)
GH47 (Glycoside Hydrolase Family 47)
PF01532 (Glyco_hydro_47)
[Graphical View]

KEGG enzyme name
mannosyl-oligosaccharide 1,2-alpha-mannosidase
mannosidase 1A
mannosidase 1B
1,2-alpha-mannosidase
exo-alpha-1,2-mannanase
mannose-9 processing alpha-mannosidase
glycoprotein processing mannosidase I
mannosidase I
Man9-mannosidase
ManI
1,2-alpha-mannosyl-oligosaccharide alpha-D-mannohydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9UKM7 MA1B1_HUMAN Hydrolysis of the terminal (1->2)-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide Man(9)(GlcNAc)(2). Endoplasmic reticulum membrane, Single-pass type II membrane protein. Calcium.

KEGG Pathways
Map code Pathways E.C.
MAP00510 N-Glycan biosynthesis
MAP00513 High-mannose type N-glycan biosynthesis
MAP01030 Glycan structures - biosynthesis 1

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00076 L00110 C00001 L00021 C00936
E.C.
Compound Calcium Man9(GlcNAc)2 H2O Man5(GlcNAc)2 alpha-D-Mannose
Type divalent metal (Ca2+, Mg2+) amide group,polysaccharide H2O amide group,polysaccharide carbohydrate
ChEBI 29108
59579
15377
28729
PubChem 271
11400707
22247451
962
71297616
185698
1fmiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Unbound
1fo2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Analogue:DMJ
1fo3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Analogue:KIF
1x9dA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Analogue:SMD Bound:HOH_5 Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [3]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1fmiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 330;ASP 463;GLU 599 THR 688(Calcium binding)
1fo2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 330;ASP 463;GLU 599 THR 688(Calcium binding) mutant deletion T241
1fo3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 330;ASP 463;GLU 599 THR 688(Calcium binding) mutant deletion T241
1x9dA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 330;ASP 463;GLU 599 THR 688(Calcium binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Fig.5, p.41295-41296
[5]
p.133

References
[1]
Resource
Comments
Medline ID
PubMed ID 10521544
Journal Glycobiology
Year 1999
Volume 9
Pages 1073-8
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.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10830477
Journal Biosci Biotechnol Biochem
Year 2000
Volume 64
Pages 675-88
Authors Ichishima E
Title Unique catalytic and molecular properties of hydrolases from Aspergillus used in Japanese bioindustries.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10995765
Journal J Biol Chem
Year 2000
Volume 275
Pages 41287-98
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.
Related PDB 1fmi 1fo2 1fo3
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 11673242
Journal Bioinformatics
Year 2001
Volume 17
Pages 965-76
Authors Jordan IK, Bishop GR, Gonzalez DS
Title Sequence and structural aspects of functional diversification in class I alpha-mannosidase evolution.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12211022
Journal Proteins
Year 2002
Volume 49
Pages 125-34
Authors Mulakala C, Reilly PJ
Title Understanding protein structure-function relationships in Family 47 alpha-1,2-mannosidases through computational docking of ligands.
Related PDB
Related UniProtKB

Comments
(2) The activated water makes a nucleophilic attack on the C1 atom of Man10.
(1) Glu599 acts as a general base, to activate a water molecule (HOH 5 in 1x9d). The water is also bound to the Ca2+.
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 [3], 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 [5] 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 [3], [5] and the structure with substrate analogue (PDB;1x9d), the catalytic reaction may proceeds as follows:
(3) Glu330 acts as a general acid, to protonate leaving O2 atom of Man7, through a water (HOH 8 in 1x9d).

Created Updated
2004-07-15 2014-07-09