EzCatDB: D00470
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DB codeD00470
RLCP classification1.30.11370.560 : Hydrolysis
CATH domainDomain 1-.-.-.-
Domain 21.50.10.50 : GlycosyltransferaseCatalytic domain
E.C.3.2.1.113

CATH domainRelated DB codes (homologues)
1.50.10.50 : GlycosyltransferaseS00051

Enzyme Name
UniProtKBKEGG

Q9UKM7
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
Mannosidase alpha class 1B member 1
Man9GlcNAc2-specific-processing alpha-mannosidase
RefSeqNP_057303.2 (Protein)
NM_016219.4 (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 NumberQ9UKM7
Entry nameMA1B1_HUMAN
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
962
22247451
71297616
185698
             
1fmiABound:_CAUnbound UnboundUnbound
1fo2ABound:_CAUnbound UnboundAnalogue:DMJ
1fo3ABound:_CAUnbound UnboundAnalogue:KIF
1x9dABound:_CAAnalogue:SMDBound:HOH 5UnboundUnbound

Active-site residues
resource
literature [3]
pdbCatalytic residuesCofactor-binding residuescomment
           
1fmiAGLU 330;ASP 463;GLU 599
THR 688(Calcium binding)
 
1fo2AGLU 330;ASP 463;GLU 599
THR 688(Calcium binding)
mutant deletion T241
1fo3AGLU 330;ASP 463;GLU 599
THR 688(Calcium binding)
mutant deletion T241
1x9dAGLU 330;ASP 463;GLU 599
THR 688(Calcium binding)
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.5, p.41295-41296
[5]p.133

references
[1]
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.
[2]
PubMed ID10830477
JournalBiosci Biotechnol Biochem
Year2000
Volume64
Pages675-88
AuthorsIchishima E
TitleUnique catalytic and molecular properties of hydrolases from Aspergillus used in Japanese bioindustries.
[3]
CommentsX-ray crystallography
PubMed ID10995765
JournalJ Biol Chem
Year2000
Volume275
Pages41287-98
AuthorsVallee F, Karaveg K, Herscovics A, Moremen KW, Howell PL
TitleStructural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases.
Related PDB1fmi,1fo2,1fo3
[4]
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.
[5]
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.

comments
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:
(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).

createdupdated
2004-07-152014-07-09


Copyright: Nozomi Nagano, JST & CBRC-AIST
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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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