EzCatDB: S00051
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DB codeS00051
RLCP classification1.30.11370.560 : Hydrolysis
CATH domainDomain 11.50.10.50 : GlycosyltransferaseCatalytic domain
E.C.3.2.1.113
CSA1dl2
MACiEM0019

CATH domainRelated DB codes (homologues)
1.50.10.50 : GlycosyltransferaseD00470

Enzyme Name
UniProtKBKEGG

P32906
Protein nameEndoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidasemannosyl-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
SynonymsEC 3.2.1.113
ER alpha-1,2-mannosidase
Man(9)-alpha-mannosidase
RefSeqNP_012665.3 (Protein)
NM_001181789.3 (DNA/RNA sequence)
PfamPF01532 (Glyco_hydro_47)
[Graphical view]
CAZyGH47 (Glycoside Hydrolase Family)

KEGG pathways
MAP codePathways
MAP00510N-Glycan biosynthesis
MAP00513High-mannose type N-glycan biosynthesis
MAP01030Glycan structures - biosynthesis 1

UniProtKB:Accession NumberP32906
Entry nameMNS1_YEAST
ActivityHydrolysis of the terminal (1->2)-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide Man(9)(GlcNAc)(2).
Subunit
Subcellular locationEndoplasmic reticulum membrane, Single-pass type II membrane protein.
CofactorCalcium.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00076L00110C00001L00021C00936
CompoundCalciumMan9(GlcNAc)2H2OMan5(GlcNAc)2alpha-D-Mannose
Typedivalent metal (Ca2+, Mg2+)amide group,polysaccharideH2Oamide group,polysaccharidecarbohydrate
ChEBI29108
59579
15377

28729
PubChem271
11400707
22247451
962
71297616
185698
             
1dl2ABound:_CAUnbound UnboundUnbound
1g6iABound:_CAUnbound UnboundAnalogue:DMJ

Active-site residues
resource
literature [11], [15]
pdbCatalytic residuesCofactor-binding residues
          
1dl2AGLU 132;ASP 275;GLU 435
THR 525(Calcium binding)
1g6iAGLU 132;ASP 275;GLU 435
THR 525(Calcium binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]p.585-586
[15]Fig.5, p.32
[16]Fig.9, p.132

references
[1]
PubMed ID7945271
JournalBiochem J
Year1994
Volume303
Pages97-103
AuthorsYoshida T, Maeda K, Kobayashi M, Ichishima E
TitleChemical modification of Penicillium 1,2-alpha-D-mannosidase by water-soluble carbodi-imide: identification of a catalytically important aspartic acid residue.
[2]
PubMed ID7726853
JournalBiochem Biophys Res Commun
Year1995
Volume209
Pages322-6
AuthorsLipari F, Gour-Salin BJ, Herscovics A
TitleThe Saccharomyces cerevisiae processing alpha 1,2-mannosidase is an inverting glycosidase.
[3]
PubMed ID8724134
JournalGlycobiology
Year1996
Volume6
Pages265-70
AuthorsScaman CH, Lipari F, Herscovics A
TitleA spectrophotometric assay for alpha-mannosidase activity.
[4]
PubMed ID8910350
JournalJ Biol Chem
Year1996
Volume271
Pages27615-22
AuthorsLipari F, Herscovics A
TitleRole 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.
[5]
PubMed ID9325167
JournalBiochem Biophys Res Commun
Year1997
Volume238
Pages779-83
AuthorsFujita A, Yoshida T, Ichishima E
TitleFive crucial carboxyl residues of 1,2-alpha-mannosidase from Aspergillus saitoi (A. phoenicis), a food microorganism, are identified by site-directed mutagenesis.
[6]
PubMed ID9356293
JournalJ Struct Biol
Year1997
Volume120
Pages69-72
AuthorsDole K, Lipari F, Herscovics A, Howell PL
TitleCrystallization and preliminary X-ray analysis of the class 1 alpha 1,2-mannosidase from Saccharomyces cerevisiae.
[7]
PubMed ID9894008
JournalBiochemistry
Year1999
Volume38
Pages1111-8
AuthorsLipari F, Herscovics A
TitleCalcium binding to the class I alpha-1,2-mannosidase from Saccharomyces cerevisiae occurs outside the EF hand motif.
[8]
PubMed ID10521544
JournalGlycobiology
Year1999
Volume9
Pages1073-8
AuthorsTremblay LO, Herscovics A
TitleCloning and expression of a specific human alpha 1,2-mannosidase that trims Man9GlcNAc2 to Man8GlcNAc2 isomer B during N-glycan biosynthesis.
[9]
PubMed ID10830477
JournalBiosci Biotechnol Biochem
Year2000
Volume64
Pages675-88
AuthorsIchishima E
TitleUnique catalytic and molecular properties of hydrolases from Aspergillus used in Japanese bioindustries.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 34-549.
Medline ID20141183
PubMed ID10675327
JournalEMBO J
Year2000
Volume19
Pages581-8
AuthorsVallee F, Lipari F, Yip P, Sleno B, Herscovics A, Howell PL
TitleCrystal structure of a class I alpha1,2-mannosidase involved in N-glycan processing and endoplasmic reticulum quality control.
Related PDB1dl2
Related UniProtKBP32906
[11]
PubMed ID10753911
JournalJ Biol Chem
Year2000
Volume275
Pages11071-4
AuthorsRomero PA, Vallee F, Howell PL, Herscovics A
TitleMutation of Arg(273) to Leu alters the specificity of the yeast N-glycan processing class I alpha1,2-mannosidase.
[12]
PubMed ID11673242
JournalBioinformatics
Year2001
Volume17
Pages965-76
AuthorsJordan IK, Bishop GR, Gonzalez DS
TitleSequence and structural aspects of functional diversification in class I alpha-mannosidase evolution.
[13]
PubMed ID11792827
JournalJ Cell Sci
Year2001
Volume114
Pages4629-35
AuthorsMassaad MJ, Herscovics A
TitleInteraction of the endoplasmic reticulum alpha 1,2-mannosidase Mns1p with Rer1p using the split-ubiquitin system.
[14]
PubMed ID11545593
JournalJ Mol Biol
Year2001
Volume312
Pages157-65
AuthorsVan Petegem F, Contreras H, Contreras R, Van Beeumen J
TitleTrichoderma reesei alpha-1,2-mannosidase: structural basis for the cleavage of four consecutive mannose residues.
[15]
CommentsX-ray crystallography (ISBN:085404826x)
JournalCarbohydrate Bioengineering
Year2002
Volume
Pages28-33
AuthorsHerscovics A, Lipari F, Sleno B, Romera PA, Vallee F, Yip P, Howell PA
TitleStructure and Function of Class I A1,2-Mannosidases Involved in Glycoprotein Biosynthesis.
Related PDB1g6i
[16]
PubMed ID12211022
JournalProteins
Year2002
Volume49
Pages125-34
AuthorsMulakala C, Reilly PJ
TitleUnderstanding protein structure-function relationships in Family 47 alpha-1,2-mannosidases through computational docking of ligands.
[17]
PubMed ID12702721
JournalJ Biol Chem
Year2003
Volume278
Pages25289-94
AuthorsTatara Y, Lee BR, Yoshida T, Takahashi K, Ichishima E
TitleIdentification of catalytic residues of Ca2+-independent 1,2-alpha-D-mannosidase from Aspergillus saitoi by site-directed mutagenesis.

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.

createdupdated
2004-08-282014-07-09
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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