DB code: S00051

RLCP classification 1.30.11370.560 : Hydrolysis
CATH domain 1.50.10.50 : Glycosyltransferase Catalytic domain
E.C. 3.2.1.113
CSA 1dl2
M-CSA 1dl2
MACiE M0019

CATH domain Related DB codes (homologues)
1.50.10.50 : Glycosyltransferase D00470

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq CAZy Pfam
P32906 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase
EC 3.2.1.113
ER alpha-1,2-mannosidase
Man(9)-alpha-mannosidase
NP_012665.3 (Protein)
NM_001181789.3 (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
P32906 MNS1_YEAST 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
1dl2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Unbound
1g6iA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Analogue:DMJ

Reference for Active-site residues
resource references E.C.
literature [11], [15]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dl2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 132;ASP 275;GLU 435 THR 525(Calcium binding)
1g6iA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 132;ASP 275;GLU 435 THR 525(Calcium binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
p.585-586
[15]
Fig.5, p.32
[16]
Fig.9, p.132

References
[1]
Resource
Comments
Medline ID
PubMed ID 7945271
Journal Biochem J
Year 1994
Volume 303
Pages 97-103
Authors Yoshida T, Maeda K, Kobayashi M, Ichishima E
Title Chemical modification of Penicillium 1,2-alpha-D-mannosidase by water-soluble carbodi-imide: identification of a catalytically important aspartic acid residue.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7726853
Journal Biochem Biophys Res Commun
Year 1995
Volume 209
Pages 322-6
Authors Lipari F, Gour-Salin BJ, Herscovics A
Title The Saccharomyces cerevisiae processing alpha 1,2-mannosidase is an inverting glycosidase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8724134
Journal Glycobiology
Year 1996
Volume 6
Pages 265-70
Authors Scaman CH, Lipari F, Herscovics A
Title A spectrophotometric assay for alpha-mannosidase activity.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8910350
Journal J Biol Chem
Year 1996
Volume 271
Pages 27615-22
Authors Lipari F, Herscovics A
Title Role of the cysteine residues in the alpha1,2-mannosidase involved in N-glycan biosynthesis in Saccharomyces cerevisiae. The conserved Cys340 and Cys385 residues form an essential disulfide bond.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9325167
Journal Biochem Biophys Res Commun
Year 1997
Volume 238
Pages 779-83
Authors Fujita A, Yoshida T, Ichishima E
Title Five crucial carboxyl residues of 1,2-alpha-mannosidase from Aspergillus saitoi (A. phoenicis), a food microorganism, are identified by site-directed mutagenesis.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9356293
Journal J Struct Biol
Year 1997
Volume 120
Pages 69-72
Authors Dole K, Lipari F, Herscovics A, Howell PL
Title Crystallization and preliminary X-ray analysis of the class 1 alpha 1,2-mannosidase from Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9894008
Journal Biochemistry
Year 1999
Volume 38
Pages 1111-8
Authors Lipari F, Herscovics A
Title Calcium binding to the class I alpha-1,2-mannosidase from Saccharomyces cerevisiae occurs outside the EF hand motif.
Related PDB
Related UniProtKB
[8]
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
[9]
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
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 34-549.
Medline ID 20141183
PubMed ID 10675327
Journal EMBO J
Year 2000
Volume 19
Pages 581-8
Authors Vallee F, Lipari F, Yip P, Sleno B, Herscovics A, Howell PL
Title Crystal structure of a class I alpha1,2-mannosidase involved in N-glycan processing and endoplasmic reticulum quality control.
Related PDB 1dl2
Related UniProtKB P32906
[11]
Resource
Comments
Medline ID
PubMed ID 10753911
Journal J Biol Chem
Year 2000
Volume 275
Pages 11071-4
Authors Romero PA, Vallee F, Howell PL, Herscovics A
Title Mutation of Arg(273) to Leu alters the specificity of the yeast N-glycan processing class I alpha1,2-mannosidase.
Related PDB
Related UniProtKB
[12]
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
[13]
Resource
Comments
Medline ID
PubMed ID 11792827
Journal J Cell Sci
Year 2001
Volume 114
Pages 4629-35
Authors Massaad MJ, Herscovics A
Title Interaction of the endoplasmic reticulum alpha 1,2-mannosidase Mns1p with Rer1p using the split-ubiquitin system.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11545593
Journal J Mol Biol
Year 2001
Volume 312
Pages 157-65
Authors Van Petegem F, Contreras H, Contreras R, Van Beeumen J
Title Trichoderma reesei alpha-1,2-mannosidase: structural basis for the cleavage of four consecutive mannose residues.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-ray crystallography (ISBN:085404826x)
Medline ID
PubMed ID
Journal Carbohydrate Bioengineering
Year 2002
Volume
Pages 28-33
Authors Herscovics A, Lipari F, Sleno B, Romera PA, Vallee F, Yip P, Howell PA
Title Structure and Function of Class I A1,2-Mannosidases Involved in Glycoprotein Biosynthesis.
Related PDB 1g6i
Related UniProtKB
[16]
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
[17]
Resource
Comments
Medline ID
PubMed ID 12702721
Journal J Biol Chem
Year 2003
Volume 278
Pages 25289-94
Authors Tatara Y, Lee BR, Yoshida T, Takahashi K, Ichishima E
Title Identification of catalytic residues of Ca2+-independent 1,2-alpha-D-mannosidase from Aspergillus saitoi by site-directed mutagenesis.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the glycosyl hydrolase family-47, with an inverting mechanism (see [2]).
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 human is included in D00470.
According to the literature [10], [15] & [16], the catalytic mechanism must be similar to that of the human counterpart (D00470 in EzCatDB).
(1) Glu435 acts as a general base, to activate a water molecule. 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.

Created Updated
2004-08-28 2014-07-09