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 29108	59579 59579	15377 15377		28729 28729
PubChem	271 271	11400707 11400707	22247451 962 22247451 962	71297616 71297616	185698 185698

1dl2A	Bound:_CA	Unbound		Unbound	Unbound
1g6iA	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	GLU 132;ASP 275;GLU 435	THR 525(Calcium binding)
1g6iA	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.

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