Information on EC 3.2.1.114 - mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
3.2.1.114
-
RECOMMENDED NAME
GeneOntology No.
mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Hydrolysis of the terminal (1->3)- and (1->6)-linked alpha-D-mannose residues in the mannosyl-oligosaccharide Man5(GlcNAc)3
show the reaction diagram
catalytic mechanism
-
Hydrolysis of the terminal (1->3)- and (1->6)-linked alpha-D-mannose residues in the mannosyl-oligosaccharide Man5(GlcNAc)3
show the reaction diagram
the conformational change of the bound mannoside to a high-energy B2,5 conformation is facilitated by steric hindrance from, and the formation of strong hydrogen bonds to, resiude D204
-
Hydrolysis of the terminal (1->3)- and (1->6)-linked alpha-D-mannose residues in the mannosyl-oligosaccharide Man5(GlcNAc)3
show the reaction diagram
reaction mechanism via glycosyl-enzyme intermediate, overview
Q99YP5
Hydrolysis of the terminal (1->3)- and (1->6)-linked alpha-D-mannose residues in the mannosyl-oligosaccharide Man5(GlcNAc)3
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of N-glycosyl bond
-
-
hydrolysis of O-glycosyl bond
-
-
-
-
hydrolysis of O-glycosyl bond
Q24451
-
PATHWAY
KEGG Link
MetaCyc Link
Metabolic pathways
-
N-Glycan biosynthesis
-
Various types of N-glycan biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
(1->3)-(1->6)-mannosyl-oligosaccharide alpha-D-mannohydrolase
Involved in the synthesis of glycoproteins.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1,3(1,6)-alpha-D-mannosidase
-
-
1,6-alpha-D-mannosidase
-
-
Afams1
Q5I5K3
-
Afams1
Aspergillus fumigatus YJ-407
Q5I5K3
-
-
alpha-1,3 mannosidase
Q99YP5
-
alpha-1,3-mannosidase
-
-
alpha-D-mannosidase II
-
-
-
-
alpha-mannosidase
Q24451
-
alpha-mannosidase
Q99YP5
-
alpha-mannosidase II
-
-
-
-
alpha-mannosidase II
-
-
alpha-mannosidase II
-
-
alpha-mannosidase III
-
-
-
-
alpha-mannosidase IIx
-
homolog to alpha-mannosidase II with different substrate specificity
alpha-mannosidase IIx
-
-
alpha1-3,6-mannosidase
-
-
-
-
Bt3991
-
-
class II alpha-D-mannosidase
-
-
class II alpha-mannosidase
-
-
class II alpha-mannosidase
-
-
class IIC alpha-mannosidase
Q5I5K3
-
class IIC alpha-mannosidase
Aspergillus fumigatus YJ-407
Q5I5K3
-
-
Drosophila GMII
Q24451
-
exo-1,3-1,6-alpha-mannosidase
-
-
-
-
GH38 alpha-mannosidase II
Q99YP5
-
GH38 enzyme
Q99YP5
-
GH38 Golgi alpha-mannosidase II
-
-
GlcNAc transferase I-dependent alpha1,3[alpha1,6]mannosidase
-
-
-
-
glycoside hydrolase
Q24451
-
GmII
-
-
Golgi alpha-mannosidase II
-
-
-
-
Golgi alpha-mannosidase II
Q9LFR0
-
Golgi alpha-mannosidase II
Q24451
-
Golgi alpha-mannosidase II
-
-
Golgi mannosidase IIx
-
close homolog to Golgi mannosidase II with different substrate specificity
human type II alpha-mannosidase
-
-
jack bean alpha-mannosidase
-
-
Man II
-
-
-
-
MAN IIx
-
-
-
-
ManII
-
-
ManIII
-
-
-
-
mannose-trimming enzyme
-
-
mannosidase II
-
-
-
-
mannosidase II
-
-
mannosidase, exo-1,3-1,6-alpha-
-
-
-
-
mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase
-
-
-
-
mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase II
-
-
neutral alpha-mannosidase
-
-
SpGH38
Q99YP5
-
additional information
-
member of glycosyl hydrolase family 38
additional information
-
Bt3991 belongs to the glycosyl hydrolase family 92, GH92
additional information
-
member of glycosyl hydrolase family 38
additional information
Q99YP5
the enzyme belongs to the family GH38 of alpha-mannosidases
additional information
-
the enzyme belongs to the glycoside hydrolase family 38
CAS REGISTRY NUMBER
COMMENTARY
349553-33-9
alpha-mannosidase III
82047-77-6
alpha-mannosidase II
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain YJ-407
UniProt
Manually annotated by BRENDA team
Aspergillus fumigatus YJ-407
strain YJ-407
UniProt
Manually annotated by BRENDA team
strain Bm-N
-
-
Manually annotated by BRENDA team
Bombyx mori Bm-N
strain Bm-N
-
-
Manually annotated by BRENDA team
; isoform GMII
SwissProt
Manually annotated by BRENDA team
alpha-mannosidase II and IIx
-
-
Manually annotated by BRENDA team
strain Mb-0503
-
-
Manually annotated by BRENDA team
Mamestra brassicae Mb-0503
strain Mb-0503
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
plant
-
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
at least 3 different forms of ManIII; Sf-9, alpha-mannosidase III
-
-
Manually annotated by BRENDA team
baculovirus-infected IPLB-SF-21AE
-
-
Manually annotated by BRENDA team
Sf-9, alpha-mannosidase III
-
-
Manually annotated by BRENDA team
Spodoptera frugiperda Sf-21
Sf-21
-
-
Manually annotated by BRENDA team
gene M1 GAS SF370
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
key enzyme in removal of mannose residues from the maturing oligosaccharide by hydrolyzing the mannosyl glycosidic bond as part of the machinery of complex carbohydrate formation
physiological function
-, Q5I5K3
the Afams1 gene, in contrast to its homologues in Saccharomyces cerevisiae or Aspergillus nidulans, is required for morphogenesis and cellular function in Aspergillus fumigatus
physiological function
-
the enzyme is important for N-glycosylation of protein in the Golgi apparatus
physiological function
Q99YP5
the enzyme is perhaps functioning in the subsequent degradation of extracellular host glycans following their initial digestion by secreted glycosidases
physiological function
Aspergillus fumigatus YJ-407
-
the Afams1 gene, in contrast to its homologues in Saccharomyces cerevisiae or Aspergillus nidulans, is required for morphogenesis and cellular function in Aspergillus fumigatus
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(Man)3GlcNAc + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
(Man)6GlcNAc + H2O
?
show the reaction diagram
-
rate at 2% of GlcNAc(Man)5GlcNAc hydrolysis
-
-
?
(Man)7GlcNAc + H2O
?
show the reaction diagram
-
rate at 3% of GlcNAc(Man)5GlcNAc hydrolysis
-
-
?
(Man)8GlcNAc + H2O
?
show the reaction diagram
-
rate at 5% of GlcNAc(Man)5GlcNAc hydrolysis
-
-
?
(Man)9GlcNAc + H2O
?
show the reaction diagram
-
rate at 6.4% of GlcNAc(Man)5GlcNAc hydrolysis
-
-
?
(Man)9GlcNAc + H2O
(Man)5GlcNAc + D-mannose
show the reaction diagram
-
hydrolysis to (Man)5GlcNAc in the presence of Fe2+, Co2+, and Mn2+. Without activating cations the main reaction product is (Man)8GlcNAc
-
-
?
2,4-dinitrophenyl alpha-D-mannopyranoside + H2O
?
show the reaction diagram
-
-
-
-
?
2,4-dinitrophenyl alpha-D-mannopyranoside + H2O
2,4-dinitrophenol + alpha-D-mannopyranose
show the reaction diagram
Q99YP5
-
-
-
?
2,4-dinitrophenyl alpha-D-mannoside + H2O
2,4-dinitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
?
2,4-dinitrophenyl-alpha-D-mannopyranoside + H2O
2,4-dinitrophenol + D-mannose
show the reaction diagram
-
-
-
-
?
2,5-dinitrophenyl-alpha-D-mannopyranoside + H2O
2,4-dinitrophenol + D-mannose
show the reaction diagram
Q24451
-
-
-
?
2,5-dinitrophenyl-alpha-D-mannopyranoside + H2O
2,5-dinitrophenol + alpha-D-mannose
show the reaction diagram
Q24451
pH 5.6, room temperature
-
-
?
2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1->2)-alpha-D-mannopyranosyl-(1->3)-[alpha-D-mannopyranosyl-(1->3)-alpha-D-mannopyranosyl-(1->6)]-beta-D-mannopyranosyl-(1->4)-2-(acetylamino)-2-deoxy-alpha-D-glucopyranose + H2O
2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1->2)-alpha-D-mannopyranosyl-(1->3)-[alpha-D-mannopyranosyl-(1->6)]-beta-D-mannopyranosyl-(1->4)-2-(acetylamino)-2-deoxy-alpha-D-glucopyranose + D-mannose
show the reaction diagram
-
-
-
-
ir
2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1->2)-alpha-D-mannopyranosyl-(1->3)-[alpha-D-mannopyranosyl-(1->3)-[alpha-D-mannopyranosyl-(1->6)]-alpha-D-mannopyranosyl-(1->6)]-beta-D-mannopyranosyl-(1->4)-2-(acetylamino)-2-deoxy-alpha-D-glucopyranose + H2O
2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl-(1->2)-alpha-D-mannopyranosyl-(1->3)-[alpha-D-mannopyranosyl-(1->3)-alpha-D-mannopyranosyl-(1->6)]-beta-D-mannopyranosyl-(1->4)-2-(acetylamino)-2-deoxy-alpha-D-glucopyranose + D-mannose
show the reaction diagram
-
-
-
-
ir
2-deoxy-2-fluoro-alpha-D-mannosyl fluoride
?
show the reaction diagram
-
wild-type and D341N mutant GMII, acts as very slow substrate of the mutant enzyme with a rate-limiting deglycosylation step
-
-
?
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
alpha-D-mannopyranose
show the reaction diagram
Q99YP5
the enzyme is only active with the alpha-1,3-linked disaccharide
-
-
?
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
2 alpha-D-mannopyranose
show the reaction diagram
-
Bt3991 displays particularly high activity against alpha-1,3-mannobiose
-
-
?
4-methyl-umbelliferyl-alpha-D-mannopyranoside + H2O
4-methyl-umbelliferone + alpha-D-mannopyranose
show the reaction diagram
-
30 min, 37C
-
-
?
4-methylumbelliferyl alpha-D-mannopyranoside + H2O
?
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannopyranoside + H2O
4-methylumbelliferol + alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannopyranoside + H2O
4-methylumbelliferol + alpha-D-mannopyranose
show the reaction diagram
Q99YP5
-
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-
-
-
-
-
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-, P27046
-
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferone + alpha-D-mannose
show the reaction diagram
-
catalytic domain of alpha-mannosidase IIx
-
-
?
4-methylumbelliferyl alpha-D-mannoside + H2O
4-methylumbelliferol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannopyranoside + H2O
4-nitrophenol + alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannopyranoside + H2O
4-nitrophenol + alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannopyranoside + H2O
4-nitrophenol + alpha-D-mannopyranose
show the reaction diagram
Q99YP5
-
-
-
?
4-nitrophenyl alpha-D-mannopyranoside + H2O
4-nitrophenol + alpha-D-mannosepyranose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-, Q9LFR0
-
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
rat
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase III
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
rate at 23.5% of GlcNAc(Man)5GlcNAc hydrolysis
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase IIx
-
-
?
4-nitrophenyl alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
Spodoptera frugiperda Sf-21, Bombyx mori Bm-N
-
-
-
-
?
4-nitrophenyl-alpha-D-mannopyranoside + H2O
4-nitrophenol + alpha-D-mannopyranose
show the reaction diagram
-
30 min, 37C
-
-
?
4-nitrophenyl-alpha-D-mannopyranoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
Q24451
30 min, 20C
-
-
?
4-nitrophenyl-alpha-D-mannoside + H2O
4-nitrophenol + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
5-fluoro-beta-L-gulosyl fluoride + H2O
?
show the reaction diagram
-
acts as slow substrate with a rate-limiting deglycosylation step, wild-type and D341N mutant GMII
-
-
?
alpha-D-Man-(1,6)-D-Man + H2O
alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
alpha-D-Manp-(1,3)-D-Manp + H2O
alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
alpha-D-Manp-(1,6)-D-Manp + H2O
alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
baker's yeast mannan + H2O
?
show the reaction diagram
-
-
-
-
?
D-Manalpha(1-2)Manalpha(1-3)Manbeta(1-4)GlcNAc + H2O
?
show the reaction diagram
-
NaBH4 reduced, poor substrate
-
-
?
D-Manalpha(1-3)Manbeta(1-4)GlcNAc + H2O
D-Manbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
NaBH4 reduced, good substrate
-
-
?
D-Manalpha(1-3)Manbeta(1-4)GlcNAc + H2O
D-Manbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
NaBH4 reduced, good substrate
NaBH4 reduced
?
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
-
-
?
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
-
-
?
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
-
-
?
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase II
-
?
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn + H2O
D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn + alpha-D-mannose
show the reaction diagram
-
i.e. glycopeptide III, derived from ovalbumin, no hydrolysis of the innermost alpha-1,6-linked or the alpha-1,2-linked mannose
i.e. glycopeptide II
?
D-Manalpha(1-6)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
D-Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
NaBH4 reduced, at lower rate than Manalpha(1-3)Manbeta(1-4)GlcNAc hydrolysis
NaBH4 reduced
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
-
-
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
-
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
-
-
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
-
-
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
preferred substrate
-
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
strict substrate specificity
final product, via GlcNAc(Man)4GlcNAc
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
removes the exposed alpha-1,3- and alpha-1,6-mannosyl residues
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
excellent substrate, removes the alpha-1,3- and alpha-1,6-mannosyl residues with preference for the alpha-1,6-linkage
final product, via GlcNAc(Man)4GlcNAc, product structure: GlcNAcManalpha(1-3)(Manalpha(1-6))ManbetaGlcNAc
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
natural substrate, involved in the processing of N-linked oligosaccharides
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
natural substrate, involved in the processing of N-linked oligosaccharides
-
-
?
GlcNAc(Man)5GlcNAc2 + H2O
GlcNAc(Man)3GlcNAc2 + D-mannose
show the reaction diagram
-
-
-
-
?
GlcNAc(Man)5GlcNAc2 + H2O
GlcNAc(Man)3GlcNAc2 + D-mannose
show the reaction diagram
-
alpha-mannosidase IIx protein
-
-
?
GlcNAcbeta(1-2)Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
?
show the reaction diagram
-
NaBH4 reduced, hydrolysis at equal rate as Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc, galactosyl and sialyl-galactosyl derivatives are substrates, too
-
-
?
GlcNAcbeta(1-6)(GlcNAcbeta(1-2))Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
?
show the reaction diagram
-
NaBH4 reduced, rate at 50% of Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc hydrolysis
-
-
?
GlcNAcMan5GlcNAc2 + H2O
?
show the reaction diagram
-
-
-
-
?
GlcNAcMan5GlcNAc2 + H2O
? + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
high mannose N-glycan + H2O
?
show the reaction diagram
Q99YP5
-
-
-
?
Man5GlcNAc2 + H2O
Man3GlcNAc2 + 2 alpha-D-mannopyranose
show the reaction diagram
-
-, the alpha-1,3-mannosidase Bt3991, while unable to hydrolyze Man9GlcNAc2, converts Man5GlcNAc2 into Man3GlcNAc2 hydrolyzing the distal alpha-1,6-mannosidic linkage in high-mannose N-glycans. The alpha-1,3-mannosidic linkages in N-glycans are available to the enzyme once the terminal alpha-1,2-linked mannosyl residues are removed
-
-
?
Manalpha(1-3)Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + H2O
Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-3)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + H2O
Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))(Xylbeta(1-4))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + H2O
Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))(Xylbeta(1-4))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + alpha-D-mannose
show the reaction diagram
-, Q9LFR0
-
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + H2O
Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + alpha-D-mannose
show the reaction diagram
-, Q9LFR0
physiological substrate, conversion by sequential removal of two alpha1,6-linked and alpha1,3-linked mannose residues from the alpha-1,6-branch of the substrate
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + H2O
Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + alpha-D-mannose
show the reaction diagram
-, Q9LFR0
conversion by sequential removal of two alpha1,6-linked and alpha1,3-linked mannose residues from the alpha-1,6-branch of the substrate
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + H2O
Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + alpha-D-mannose
show the reaction diagram
-, Q9LFR0
-
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
recombinant alpha-mannosidase IIx, expressed in CHO cells, hydrolyzes 2 peripheral Manapha(1-6) and Manalpha(1-3) residues, alpha-mannosidase IIx, M6Gn2 is the primary target in vivo, integral part of N-glycan biosynthesis
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-6)(Manalpha(1-3))D-Manalpha(1-6)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
NaBH4 reduced
NaBH4 reduced
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + H2O
Manalpha(1-3)Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-6)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
-
-
-
-
Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-6)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
NaBH4 reduced, cleaves the Manalpha(1-6)Man linkage only after its Manalpha(1-3) residue is removed
NaBH4 reduced, no product: Manalpha(1-3)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc
?
Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + H2O
Manalpha(1-3)Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-pyridylaminoside + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
-
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase II
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
acts after GlcNAc transferase I to remove the alpha-1,3- and alpha-1,6-linked mannose residue
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
non-reduced and NaBH4 reduced substrate, removes the alpha-1,3- and alpha-1,6-mannosyl residues with preference for the alpha-1,6-linked mannose residue on the alpha-1,6-linked mannose arm, via GlcNAc(Man)4(GlcNAc)2
-
-
-
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase II, biosynthesis of N-glycans
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
involved in N-glycan maturation, acts after GlcNAc transferase I to remove 2 mannose residues to form GlcNAc(Man)3(GlcNAc)2 prior to extension into complex N-glycans
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
N-glycosylation pathway
-
?
ovalbumin + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenyl-alpha-D-mannopyranoside + H2O
p-nitrophenol + alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
pyridylaminated (Man)5(GlcNAc)2 + H2O
pyridylaminated (Man)3(GlcNAc)2 + alpha-D-mannose
show the reaction diagram
-
via a (Man)4(GlcNAc)2 intermediate
-
?
pyridylaminated (Man)5(GlcNAc)2 + H2O
pyridylaminated (Man)3(GlcNAc)2 + alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase III
-
?
pyridylaminated (Man)5(GlcNAc)2 + H2O
pyridylaminated (Man)3(GlcNAc)2 + alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase III
-
?
pyridylaminated D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
pyridylaminated D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
-
-
?
pyridylaminated D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
pyridylaminated D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
via the intermediate product GlcNAc(Man)4(GlcNAc)2, the alpha-1,6-linked mannosyl residue is removed first, then the 1,3-linked
-
?
pyridylaminated D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
pyridylaminated D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
-
dependent on the prior action of N-acetylglucosaminyl transferase I on (Man)5(GlcNAc)2
-
?
pyridylaminated D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
pyridylaminated D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
Spodoptera frugiperda Sf-21
-
-
-
?
pyridylaminated D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
pyridylaminated D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
Bombyx mori Bm-N
-
via the intermediate product GlcNAc(Man)4(GlcNAc)2, the alpha-1,6-linked mannosyl residue is removed first, then the 1,3-linked, dependent on the prior action of N-acetylglucosaminyl transferase I on (Man)5(GlcNAc)2
-
?
pyridylaminated D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
pyridylaminated D-Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + alpha-D-mannose
show the reaction diagram
Mamestra brassicae Mb-0503
-
-
-
?
R-Manalpha(1-6)(Manalpha(1-3))Manbeta(1-4)GlcNAc + H2O
?
show the reaction diagram
-
-
-
-
?
yeast mannan + H2O
?
show the reaction diagram
-
-
-
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn + H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn + alpha-D-mannose
show the reaction diagram
-
processing of asparagine-linked oligosaccharides by alpha-D-mannosidase dependent on the prior action of UDP-GlcNAc:alpha-D-mannoside beta2-N-acetylglucosaminyltransferase I, removes 2 mannosyl residues, via GlcNAc(Man)4(GlcNAc)2Asn
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
substrate specificity, overview
-
-
-
additional information
?
-
-, Q9LFR0
substrate specificity, overview
-
-
-
additional information
?
-
-
domain structure
-
-
-
additional information
?
-
-, P27046
domain structure
-
-
-
additional information
?
-
-
not: (Man)5(GlcNAc)2
-
-
-
additional information
?
-
-
not: (Man)5(GlcNAc)2
-
-
-
additional information
?
-
-
not: Glc3(Man)9GlcNAc
-
-
-
additional information
?
-
-
not: 4-nitrophenyl alpha-mannoside
-
-
-
additional information
?
-
-
not: D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-4))[GlcNAcbeta(1-4)(GlcNAcbeta(1-2))Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc, GlcNAcbeta(1-2)Manalpha(1-3)(Manalpha(1-6))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc, GlcNAcbeta(1-4)Manalpha(1-3)(Manalpha(1-6))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc, all sodium borate reduced
-
-
-
additional information
?
-
-
enzyme/active site structure and substrate binding, catalytic mechanism
-
-
-
additional information
?
-
-
not: (Man)9GlcNAc
-
-
-
additional information
?
-
-
not: (Man)9GlcNAc
-
-
-
additional information
?
-
-
not: Manalpha(1-6)(R-Manalpha(1-3))Manbeta(1-4)GlcNAc
-
-
-
additional information
?
-
-
not: GlcNAc(Man)3GlcNAc
-
-
-
additional information
?
-
-
not: (Man)5GlcNAc
-
-
-
additional information
?
-
-
not: (Man)5GlcNAc
-
-
-
additional information
?
-
-
substrate specificity, hydrolysis mechanism of branched oligosaccharides
-
-
-
additional information
?
-
-
alpha-mannosidase III hydrolyzes (Man)5-9(GlcNAc)2, not: GlcNAc(Man)5(GlcNAc)2
-
-
-
additional information
?
-
-
involved in asparagine-linked oligosaccharide processing
-
-
-
additional information
?
-
-
required in the maturation of asparagine-linked oligosaccharides in the Golgi complex
-
-
-
additional information
?
-
-
biosynthesis of complex-type N-linked oligosaccharides of glycoproteins
-
-
-
additional information
?
-
-
alpha-mannosidase III probably provides an alternate N-glycan processing pathway in Sf-9 cells
-
-
-
additional information
?
-
-
function in Golgi membranes: presumably glycopolymer metabolism
-
-
-
additional information
?
-
-
Man II catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures
-
-
-
additional information
?
-
P27046
Man II catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures
-
-
-
additional information
?
-
-
involved in trimming reactions in N-glycan maturation in the Golgi complex
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
study of biosynthesis and processing of alpha-mannosidase III
-
-
-
additional information
?
-
-
Co2+ regulates the substrate specificity, overview
-
-
-
additional information
?
-
-, Q9LFR0
Golgi alpha-mannosidase II is a key enzyme in the formation of complex N-glycans in plants
-
-
-
additional information
?
-
-
the exo-type cytosolic class II enzyme cleaves off alpha-1,2-, alpha-1,3-, and alpha-1,6-mannose residues
-
-
-
additional information
?
-
-
in vitro hydrolysis of high-mannose type N-glycans, removal of terminal alpha-1,2-mannose residues, substrate specificity and isomeric substrate/product structures, overview
-
-
-
additional information
?
-
-
MII and alpha-mannosidase IIx function in N-glycan processing in a similar manner
-
-
-
additional information
?
-
-
co-expression of beta1,4-N-acetylglucosaminyltransferase III-ManIII and ManII, or of beta1,4-N-acetylglucosaminyltransferase III and ManII leads to the formation of bisected non-fucosylated glycans of the complex type
-
-
-
additional information
?
-
-
MII and alpha-mannosidase IIx function in N-glycan processing in a similar manner. Alpha-mannosidase IIx shows no reactivity to high-mannose-type carbohydrates
-
-
-
additional information
?
-
-
about 80-fold preference of isoform GMII for the cleavage of substrates containing a nonreducing beta-(1,2)-linked GlcNAc group
-
-
-
additional information
?
-
-
Bt1769, Bt3858 and Bt3991 are alpha-1,3-mannosidases that display particularly high activity against alpha-1,3-mannobiose
-
-
-
additional information
?
-
-
GMII is involved in the creation of glycoproteins that contain complex carbohydrates. It is responsible for the formation of the core trimannose structure to which all complex carbohydrates are appended. It catalyses the hydrolysis of an alpha(1,6)- and an alpha(1,3)-linked mannose from GlcNAc-Man5-GlcNAc2 to form GlcNAc-Man3-GlcNAc2-Asn-X
-
-
-
additional information
?
-
Q99YP5
higher eukaryotic GH38 alpha-mannosides play a key role in the modification and diversification of hybrid N-glycans, processes with strong cellular links to cancer and autoimmune disease
-
-
-
additional information
?
-
-
alpha-1,3-mannosidases, Bt3858 and Bt1769, convert Man4GlcNAc2 to Man3GlcNAc2, but do not attack Man5GlcNAc2, indicating that these enzymes cannot tolerate alpha-1,6-Man side chains
-
-
-
additional information
?
-
Q99YP5
SpGH38 is an alpha-mannosidase with specificity for alpha-1,3 mannosidic linkages, active site structure, overview
-
-
-
additional information
?
-
-
the cleavage mechanism involves formation of a covalent glycosyl-enzyme intermediate and results in net retention of configuration
-
-
-
additional information
?
-
Spodoptera frugiperda Sf-21, Bombyx mori Bm-N
-
not: (Man)5(GlcNAc)2
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose + H2O
alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl alpha-D-mannopyranoside + H2O
?
show the reaction diagram
-
-
-
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
natural substrate, involved in the processing of N-linked oligosaccharides
-
?
GlcNAc(Man)5GlcNAc + 2 H2O
GlcNAc(Man)3GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
natural substrate, involved in the processing of N-linked oligosaccharides
-
-
?
GlcNAcMan5GlcNAc2 + H2O
? + alpha-D-mannose
show the reaction diagram
-
-
-
-
?
high mannose N-glycan + H2O
?
show the reaction diagram
Q99YP5
-
-
-
?
Man5GlcNAc2 + H2O
Man3GlcNAc2 + 2 alpha-D-mannopyranose
show the reaction diagram
-
-
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + H2O
Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-1-Asn + alpha-D-mannose
show the reaction diagram
-, Q9LFR0
physiological substrate, conversion by sequential removal of two alpha1,6-linked and alpha1,3-linked mannose residues from the alpha-1,6-branch of the substrate
-
-
?
Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)(Manalpha(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase IIx, M6Gn2 is the primary target in vivo, integral part of N-glycan biosynthesis
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
alpha-mannosidase II, biosynthesis of N-glycans
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
involved in N-glycan maturation, acts after GlcNAc transferase I to remove 2 mannose residues to form GlcNAc(Man)3(GlcNAc)2 prior to extension into complex N-glycans
-
?
Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 H2O
Manalpha(1-6)[GlcNAcbeta(1-2)Manalpha(1-3)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + 2 alpha-D-mannose
show the reaction diagram
-
N-glycosylation pathway
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
involved in asparagine-linked oligosaccharide processing
-
-
-
additional information
?
-
-
required in the maturation of asparagine-linked oligosaccharides in the Golgi complex
-
-
-
additional information
?
-
-
biosynthesis of complex-type N-linked oligosaccharides of glycoproteins
-
-
-
additional information
?
-
-
alpha-mannosidase III probably provides an alternate N-glycan processing pathway in Sf-9 cells
-
-
-
additional information
?
-
-
function in Golgi membranes: presumably glycopolymer metabolism
-
-
-
additional information
?
-
-
Man II catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures
-
-
-
additional information
?
-
P27046
Man II catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures
-
-
-
additional information
?
-
-
involved in trimming reactions in N-glycan maturation in the Golgi complex
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
asparagine-linked glycoprotein biosynthesis
-
-
-
additional information
?
-
-
study of biosynthesis and processing of alpha-mannosidase III
-
-
-
additional information
?
-
-
Co2+ regulates the substrate specificity, overview
-
-
-
additional information
?
-
-, Q9LFR0
Golgi alpha-mannosidase II is a key enzyme in the formation of complex N-glycans in plants
-
-
-
additional information
?
-
-
the exo-type cytosolic class II enzyme cleaves off alpha-1,2-, alpha-1,3-, and alpha-1,6-mannose residues
-
-
-
additional information
?
-
-
MII and alpha-mannosidase IIx function in N-glycan processing in a similar manner
-
-
-
additional information
?
-
-
Bt1769, Bt3858 and Bt3991 are alpha-1,3-mannosidases that display particularly high activity against alpha-1,3-mannobiose
-
-
-
additional information
?
-
-
GMII is involved in the creation of glycoproteins that contain complex carbohydrates. It is responsible for the formation of the core trimannose structure to which all complex carbohydrates are appended. It catalyses the hydrolysis of an alpha(1,6)- and an alpha(1,3)-linked mannose from GlcNAc-Man5-GlcNAc2 to form GlcNAc-Man3-GlcNAc2-Asn-X
-
-
-
additional information
?
-
Q99YP5
higher eukaryotic GH38 alpha-mannosides play a key role in the modification and diversification of hybrid N-glycans, processes with strong cellular links to cancer and autoimmune disease
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
strongly activates, 1 mM, 13fold
Ca2+
-
7% activation at 1 mM
Cd2+
-
preferred divalent cation
Co2+
-
activation
Co2+
-
alpha-mannosidase III, cobalt-dependent
Co2+
-
activation; alpha-mannosidase III, cobalt-dependent
Co2+
-
preferred divalent cation
Co2+
-
120% activation at 1 mM, not essential
Co2+
-
activates, responsible for regulation of substrate specificity
Co2+
-
-
Fe2+
-
14% activation at 1 mM
Fe2+
-
is more activated by Fe2+ than Co2+
Mn2+
-
alpha-mannosidase III, activates to a lesser extend than Co2+
Ni2+
-
alpha-mannosidase III, little activation
Zn2+
-
activation
Zn2+
-
active site coordination to Zn2+
Zn2+
Q9LFR0
the recombinant GMII contains zinc in a stoichiometric amount
Zn2+
-
GMII contains a Zn atom which forms contacts with substrate analogues, stabilizes catalytic intermediates, and other inhibitors observed in the active site
Zn2+
-
is involved in the catalytic activity of the enzyme and in the strong binding of inhibitors
Zn2+
-
di-epi-swainsonine has only a single hydroxyl group at C-8 interacting with the zinc ion of the enzyme
Zn2+
-
crystallization data
Zn2+
Q99YP5
involved in catalysis
Zn2+
-
contains zinc
Mn2+
-
-
additional information
-
not activated by Mg2+, Mn2+; not activated by Na+
additional information
-
not activated by Ba2+; not activated by Mg2+, Mn2+; not activated by Zn2+
additional information
-
no metal ion requirement; not activated by Ca2+; not activated by Co2+; not activated by Mg2+, Mn2+; not activated by Zn2+
additional information
-
no metal ion requirement; not activated by Ca2+; not activated by Mg2+, Mn2+
additional information
-
no metal ion requirement; not activated by Ca2+; not activated by Co2+; not activated by Mg2+, Mn2+; not activated by Sr2+; not activated by Zn2+
additional information
-
the enzyme is not affected by Mn2+
additional information
-
does not need Ca2+ or any other metal cofactor of those tested
additional information
Q9LFR0
no effect on recombinant GMII through Ca2+, Co2+, Mn2+, Ni2+, and Zn2+
additional information
-
no effect with Zn2+, Ca2+, and Mg2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-allyl-ester-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-benzylamino)cyclopentane
-
-
(1R,2R,3R,4S,5R)-4-amino-5-methoxycyclopentane-1,2,3-triol
-
;
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-allyl ester benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-benzylamino)cyclopentane
-
-
(1R,2R,3S,4R,5R)-5-aminocyclopentane-1,2,3,4-tetrol
-
-
(1R,2S,3R,4R,5R)-5-aminocyclopentane-1,2,3,4-tetraol
-
-
(1R,2S,8aS)-1,2-dihydroxyoctahydrothieno[1,2-a]thiopyranium chloride
-
good inhibitor, lacks a hydroxyl group at C-5, more than 140fold better inhibitor of GMII than di-epi-swainsonine
(1R,6R,7R,8S)-7,8-dihydroxy-5-thia-1-thioniabicyclo[4.3.0]nonane chloride
-
synthetic inhibitor, selective and potent inhibition at 1 mM, 97% inhibition of the activity of the liver lysosomal fraction at pH 4.0, 100% at pH 6.5
(1S,2R,5R,8R,8aR)-5-[2-(4-tert-butylphenyl)ethyl]octahydroindolizine-1,2,8-triol
-
-
(1S,2R,5S,8R,8aR)-5-[2-(4-tert-butylphenyl)ethyl]octahydroindolizine-1,2,8-triol
-
-
(1S,2R,6R,7R,8S,8aS)-octahydroindolizine-1,2,6,7,8-pentol
-
most active
(1S,2R,8R,8aR)-octahydroindolizine-1,2,8-triol
-
-
(2R,3R,4R,5R)-2-(hydroxymethyl)piperidine-3,4,5-triol
-
-
(2R,3R,4R,5R)-5-amino-2-(hydroxymethyl)piperidine-3,4-diol
-
-
(2R,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2-([[(1S)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2-[[((1R)-2-hydroxy-1-[4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl]ethyl)amino] methyl]pyrrolidine-3,4-diol
-
inhibits the proliferation of primary cells and cell lines of different origins, irrespective of Bcl-2 expression levels, inducing a G2/Mcell cycle arrest and by modification of genes involved in cell cycle progression and survival, IC50 in vivo and cytotoxic effects in different cell lines, overview
(2R,3R,4S)-2[([(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]amino)-methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-1-[1,1'-biphenyl]-4-yl-2-hydroxyethyl)amino]-methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-2-hydroxy-1-(4-(phenylmethoxy)phenyl)ethyl)amino]methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-2-hydroxy-1-[4-(2-thienyl)phenyl]ethyl)-amino]methyl]pyrrolidine-3,4-diol
-
-
(2R,3R,4S)-2[[((1R)-2-hydroxy-1-[4-(prop-2-enyloxy)phenyl]-ethyl)amino]methyl] pyrrolidine-3,4-diol
-
-
(2R,3R,4S,5R)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-5-methylpyrrolidine-3,4-diol
-
-
(2R,3R,4S,5S)-6-amino-2-(hydroxymethyl)-2,3,4,5-tetrahydropyridine-3,4,5-triol
-
-
(2R,3S,4R)-2-[(1R)-1-hydroxyethyl]pyrrolidine-3,4-diol
-
most active
(2R,3S,4S)-1-[(2S,3S)-2,4-dihydroxy-3-(sulfooxy)butyl]-3,4-dihydroxy-2-(hydroxymethyl)tetrahydrothiophenium
-
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
(2S,3R,4S)-2-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]pyrrolidine-3,4-diol
-
-
(3R,4R)-4-aminopyrrolidin-3-ol
-
-
(3R,4R,5R)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
-
(3R,4R,5R)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
competitive inhibitor
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
competitve inhibitor
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxy-1-methylpyrrolidin-2-one
-
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxypyrrolidin-2-one
-
-
(3S,4S,5R,6R,E)-3,4,5-trihydroxy-6-(hydroxymethyl)piperidin-2-one O-4-chlorophenylcarbamoyl oxime
Q24451
-
(5R,6R,7S,8R)-5-methyl-1,5,6,7,8,8a-hexahydrotetrazolo[1,5-a]pyridine-6,7,8-triol
-
-
(5R,6R,7S,8S)-5-(hydroxymethyl)-1,5,6,7,8,8a-hexahydroimidazo[1,2-a]pyridine-6,7,8-triol
-
-
(RS)-2-phenylethyl alpha-D-mannopyranosyl sulfoxide
-
-
-
1,4-Dideoxy-1,4-imino-D-mannitol
-
-
1,4-Dideoxy-1,4-imino-D-mannitol
-
-
1,4-Dideoxy-1,4-imino-D-mannitol
-
much less effective than swainsonine
1,4-Dideoxy-1,4-imino-D-mannitol
-
-
1,4-Dideoxy-1,4-imino-D-mannitol
-
-
1-(4-methylphenyl)-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
-
-
1-(4-tert-butylphenyl)-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
-
-
1-(4-tert-butylphenyl)-2-[(1S,2R,5S,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
-
1-deoxyamino-cyclopentitetrol
-
-
1-deoxyaminocyclopentitetrol
-
structural basis of the inhibition of Golgi alpha-mannosidase II and the role of the thiomethyl moiety in ligand-protein interactions, overview
1-deoxyaminocyclopentitetrol
-
poor inhibitor
1-deoxymannojirimycin
-
more inhibitory than kifunensine, mode of binding
1-deoxymannojirimycin
-
0.4 mM, 50% inhibition
1-deoxymannojirimycin
-
complete inhibition at 0.5 mM
1-deoxymannojirimycin
-
61% inhibition of the activity of the liver lysosomal fraction at pH 4.0, 37% at pH 6.5, at 1 mM
1-phenyl-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
-
-
2-deoxy-2-fluoro-alpha-D-mannosyl fluoride
-
reversible, D341N mutant GMII
2-phenylethyl alpha-D-mannopyranosyl sulfone
-
-
-
5-fluoro-beta-L-gulosyl fluoride
-
reversible, wild-type and D341N mutant GMII, inhibits only at low assay temperatures, acts as slow substrate at 37C
5-thio-alpha-D-mannopyranosylamine
-
-
8,8a-di-epi-swainsonine
-
-
8-epi-lentiginosine
-
-
8a-epi-swainsonine
-
-
alpha-1,6-linked trisaccharide of mannose
-
1.5 mM, 40% inhibition
-
benzyl alpha-D-mannopyranosyl sulfone
-
-
-
Cu2+
-
1 mM, 91-93% inhibition; strong
Cu2+
-
1 mM, 50% inhibition
Cu2+
-
0.2 mM CuCl2, 75% inhibition
Cu2+
-
20 mM, 90% inhibition
Cu2+
-
0.1 mM, 90% inhibition of GlcNAc(Man)5(GlcNAc)2 hydrolysis, 0.01 mM, 50% inhibition of 4-nitrophenyl alpha-D-mannoside hydrolysis; strong
Cu2+
-
complete inhibition at 1 mM
Cu2+
Q9LFR0
over 97% inhibition of the recombinant GMII at 1 mM
Cu2+
-
completely inhibits
D-Mannonolactam amidrazone
-
broad spectrum mannosidase inhibitor, strong; IC50: 400 nM
D-Mannonolactam amidrazone
-
broad spectrum mannosidase inhibitor, strong; equally as effective as mannostatin A, IC50: 90-100 nM
deoxymannojirimycin
Q24451
-
di-epi-swainsonine
-
weak inhibitor
diastereomer of salacinol
-
-
diastereomer of seleno-salacinol
-
-
EDTA
-
20 mM, 20% inhibition
EDTA
-
alpha-mannosidase III, 1 mM, 90% inhibition of 4-nitrophenyl alpha-D-mannoside hydrolysis, 5 mM, complete inhibition of (Man)5(GlcNAc)2-PA hydrolysis
EDTA
-
26% inhibition at 1 mM
Fe2+
-
1 mM, 70-76% inhibition; strong
-
Fe2+
-
strong
-
Fe3+
-
less potent inhibitor than Fe2+ and Cu2+, 1 mM, 24-30% inhibition
-
gluco-hydroxyiminolactam
Q24451
-
glucoimidazole
Q24451
-
guanidinium hydrochloride
-
the enzyme loses 54% and 70% of the original activity in 0.5 M and 1.0 M guanidinium hydrochloride, respectively. Irreversible denaturation at higher concentration of 6 M of guanidinium hydrochloride, kinetics, overview. The protein almost completely unfolds in 4.0 M guanidinium hydrochloride
hydroxyiminolactam
-
-
-
kifunensine
-
weak, mode of binding
kifunensine
-
complete inhibition at 0.5 mM
Mannose
-
250 mM, 30% inhibition
Mannostatin A
-
cyclopentanol structure containing thiomethyl and amino functional groups, in vivo and in vitro
Mannostatin A
-
cyclopentanol structure containing thiomethyl and amino functional groups, in vivo and in vitro; potent inhibitor, equally effective as D-mannonolactam amidrazone
Mannostatin A
-
cyclopentanol structure containing thiomethyl and amino functional groups, in vivo and in vitro
Mannostatin A
-
cyclopentanol structure containing thiomethyl and amino functional groups, in vivo and in vitro; very potent inhibitor, competitive, IC50: about 10 nM with 4-nitrophenyl alpha-D-mannoside as substrate, about 90 nM with GlcNAc(Man)5GlcNAc as substrate, equally potent as swainsonine
Mannostatin A
-
; structural basis of the inhibition of Golgi alpha-mannosidase II and the role of the thiomethyl moiety in ligand-protein interactions, overview
Mannostatin A
-
; strong inhibitor, reversible, competitive
Mannostatin A
-
-
mannostatin B
-
; strong inhibitor, reversible, competitive
meso-aminocyclopentitretrol
-
-
N-benzyl mannostatin A
-
structural basis of the inhibition of Golgi alpha-mannosidase II and the role of the thiomethyl moiety in ligand-protein interactions, overview
N-benzyl-mannostatin
-
-
N-octyl-6-epi-valienamine
Q24451
-
N-[(R)-amino(phenyl)methyl]-5-thio-alpha-D-mannopyranosylamine
-
-
p-Chloromercuriphenylsulfonate
-
-
p-Chloromercuriphenylsulfonate
-
1 mM, 80% inhibition
seleno-salacinol
-
-
swainsonine
-
mode of binding; very strong
swainsonine
-
200 nM, 50% inhibition; i.e. (1S,2R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizidine; very strong
swainsonine
-
200 nM, 50% inhibition; kinetics, in vivo and in vitro, partially reversible depending on inhibitor concentration
swainsonine
-
i.e. (1S,2R,8R,8aR)-trihydroxyindolizidine; very strong
swainsonine
-
very strong
swainsonine
-
30 nM, 85% inhibition
swainsonine
-
20 nM, 50% inhibition
swainsonine
-
inhibits both alpha-mannosidase II and IIx, the latter is less sensitive
swainsonine
-
alpha-mannosidase III, IC50: 10 nM
swainsonine
-
potent inhibition at 1 mM, 100% inhibition of the activity of the liver lysosomal fraction at pH 4.0, 95% at pH 6.5
swainsonine
Q9LFR0
50% inhibition of recombinant GMII at 18 nM
swainsonine
-
disrupts enzyme activity, whereby inducing a novel class of hybrid-type glycosylation containing a partially processed mannose moiety
swainsonine
-
most active
swainsonine
Q99YP5
binding structure, overview
swainsonine
-
most powerful inhibitor
Zn2+
-
10 mM: 40% inhibition, 2.5 mM: no inhibition
Zn2+
-
alpha-mannosidase III
Zn2+
-
9% inhibition at 1 mM
[[(3S,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)piperidin-2-ylidene]amino] N-(4-chlorophenyl)carbamate
Q24451
-
additional information
-
not inhibited by Co2+, Zn2+; not inhibited by EDTA; not inhibited by Tris-Cl, iodoacetamide, alpha-methylmannoside; not inhibited by Tris-maleate
-
additional information
-
not inhibited by chelating agents, 0.1 mM 1,10-phenanthroline, 1 mM 2,2'-dipyridyl, 250 mM glucose, 250 mM galactose; not inhibited by EDTA; not inhibited by Mn2+, Mg2+
-
additional information
-
not inhibited by EDTA
-
additional information
-
not inhibited by castanospermine, deoxynojirimycin; not inhibited by deoxymannojirimycin
-
additional information
-
not inhibited by N-acetylmannostatin A
-
additional information
-
not inhibited by Tris-maleate
-
additional information
-
not inhibited by Co2+, Zn2+; not inhibited by deoxymannojirimycin; not inhibited by EDTA; not inhibited by EGTA, 6-epicastanospermine, 2-episwainsonine, a trisaccharide of mannose residues linked in alpha-1,2-linkages, a tetrasaccharide of mannose with the nonreducing mannose linked in alpha-1,3-linkage to an alpha-1,2-linked trisaccharide of mannose; not inhibited by Mn2+, Mg2+
-
additional information
-
not inhibited by N-acetylmannostatin A
-
additional information
-
not inhibited by Ca2+; not inhibited by Mn2+, Mg2+
-
additional information
-
-
-
additional information
-
not inhibited by Mn2+, Mg2+
-
additional information
-
not inhibited by EDTA
-
additional information
-
effect of tunicamycin and castanospermine on the production of the 3 forms of alpha-mannosidase III
-
additional information
-
simulations of ligand/inhibitor binding
-
additional information
Q9LFR0
no inhibition of recombinant GMII by EDTA
-
additional information
-
inhibitor design and synthesis, and cytototxic effect in vivo, overview. 2-[(Benzylamino)methyl]pyrrolidine-3,4-diol derivatives as alpha-mannosidase inhibitors and with antitumor activities against hematological and solid malignancies
-
additional information
-
inhibitor synthesis, overview
-
additional information
-
not inhibited by alpha-D-mannose
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
activation
ATP
-
1 mM, 27% activation
Bovine serum albumin
-
0.125 mg/l, 35% activation
-
CMP
-
1 mM, 25% activation
dithiothreitol
-
activation
Triton X-100
-
activation, 0.15-0.2%
Triton X-100
-
25-30% activation, 0.05%
Triton X-100
-
omission results in 40% decrease of activity
Triton X-100
-
-
fucose
-
250 mM, 15-20% activation
additional information
-
not activated by glucose, galactose, AMP, ADP, GMP, GDP, GTP, CDP, CTP, UMP, UDP, UTP, cAMP, cGMP
-
additional information
-
no effect with EDTA
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.05
-
2,4-dinitrophenyl alpha-D-mannoside
-
pH 5.6, 37C, D341N mutant GMII
5.5
-
2,4-dinitrophenyl alpha-D-mannoside
-
pH 5.6, 37C, wild-type GMII
25
-
2-deoxy-2-fluoro-alpha-D-mannosyl fluoride
-
pH 5.6, 37C, above, wild-type GMII
9
-
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
-
pH 7.0, 37C, Bt3991
27
-
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
Q99YP5
pH 6.8, 37C, recombinant enzyme
3.6
-
4-methylumbelliferyl alpha-D-mannopyranoside
Q99YP5
pH 6.8, 37C, recombinant enzyme
0.55
-
4-methylumbelliferyl-alpha-D-mannopyranoside
-
extracted from endothelial cells HCEC
0.65
-
4-methylumbelliferyl-alpha-D-mannopyranoside
-
extracted from human glioblastoma cells LNZ308
1.065
-
4-methylumbelliferyl-alpha-D-mannopyranoside
-
extracted from human glioblastoma cells LN18
2.7
-
4-nitrophenyl alpha-D-mannopyranoside
-
pH 7.0, 37C, Bt3991
30
-
4-nitrophenyl alpha-D-mannoside
-
-
40
-
4-nitrophenyl alpha-D-mannoside
-
intact 124 kDa Man II and chymotrypsin-cleaved 110 kDa catalytic subunit
0.2
-
5-fluoro-beta-L-gulosyl fluoride
-
pH 5.6, 37C, wild-type GMII
14
-
alpha-D-Man-(1,6)-D-Man
-
-
0.2
-
D-Manalpha(1-6)(Manalpha(1-3))Manalpha(1-6)(GlcNAcbeta(1-2)Manalpha(1-3))Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc-Asn
-
i.e. glycopeptide III
1.25
-
Manalpha(1,6)(Manalpha(1,3))Manbeta(1,4)GlcNAcbeta(1,4)GlcNAc
-
NaBH4 reduced; pH 5, 37C
1.25
-
Manalpha(1,6)(Manalpha(1,3))Manbeta(1,4)GlcNAcbeta(1,4)GlcNAc
-
NaBH4 reduced
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.048
-
2,4-dinitrophenyl alpha-D-mannoside
-
pH 5.6, 37C, D341N mutant GMII
8.6
-
2,4-dinitrophenyl alpha-D-mannoside
-
pH 5.6, 37C, wild-type GMII
4.67
-
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
-
pH 7.0, 37C, Bt3991
6.4
-
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
Q99YP5
pH 6.8, 37C, recombinant enzyme
0.03
-
4-methylumbelliferyl alpha-D-mannopyranoside
Q99YP5
pH 6.8, 37C, recombinant enzyme
0.0025
-
4-nitrophenyl alpha-D-mannopyranoside
-
pH 7.0, 37C, Bt3991
0.0051
-
5-fluoro-beta-L-gulosyl fluoride
-
pH 5.6, 37C, wild-type GMII
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.01
-
2,4-dinitrophenyl alpha-D-mannopyranoside
Q99YP5
pH 6.8, 37C, recombinant enzyme
284164
0.24
-
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
Q99YP5
pH 6.8, 37C, recombinant enzyme
293929
0.52
-
3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose
-
pH 7.0, 37C, Bt3991
293929
0.0009
-
4-nitrophenyl alpha-D-mannopyranoside
-
pH 7.0, 37C, Bt3991
214882
54
-
4-nitrophenyl alpha-D-mannoside
-
recombinant enzyme, in 50 mM sodium phosphate buffer, pH 6.5, at 65C
195542
351
-
4-nitrophenyl alpha-D-mannoside
-
native enzyme, in 50 mM sodium phosphate buffer, pH 6.5, at 65C
195542
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00322
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-allyl ester benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.00051
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.00091
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.00053
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.00052
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.00088
-
(1R,2R,3R,4R,5S)-1-(methylthio)-2,3,4-trihydroxy-5-(N-benzylamino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
7.6e-05
-
(1R,2R,3R,4S,5R)-4-amino-5-methoxycyclopentane-1,2,3-triol
-
;
0.0044
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-allyl ester benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.0076
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-bromo-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.0081
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-chloro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.006
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-fluoro-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.0066
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-(p-methoxy-benzyl)amino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.01
-
(1R,2R,3R,4S,5S)-1,2,3,4-tetrahydroxy-5-(N-benzylamino)cyclopentane
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
0.0003
-
(1R,2R,3S,4R,5R)-5-aminocyclopentane-1,2,3,4-tetrol
-
-
0.0003
-
(1R,2S,3R,4R,5R)-5-aminocyclopentane-1,2,3,4-tetraol
-
-
2e-05
-
(1S,2R,8R,8aR)-octahydroindolizine-1,2,8-triol
-
20C, pH 6.8
0.067
-
(2R,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
20C, pH 6.8
0.000135
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
0.0233
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
extracted from endothelial cells HCEC
0.0325
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
extracted from human glioblastoma cells LN18
0.0415
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
extracted from human glioblastoma cells LNZ308
0.067
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
0.001
-
(3R,4R,5R)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
20C, pH 6.8
0.022
-
(3R,4R,5R)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
20C, pH 6.8
0.000206
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
-
0.00055
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
extracted from human glioblastoma cells LNZ308
0.00067
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
extracted from endothelial cells HCEC
0.001
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
-
0.0032
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
extracted from human glioblastoma cells LN18
0.004
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
-
0.022
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
-
0.52
-
(3S,4S,5R,6R,E)-3,4,5-trihydroxy-6-(hydroxymethyl)piperidin-2-one O-4-chlorophenylcarbamoyl oxime
Q24451
-
0.0027
-
1-(4-methylphenyl)-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone, 1-(4-tert-butylphenyl)-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
pH 5.75, 25C
-
0.265
-
1-deoxyamino-cyclopentitetrol
-
-
0.265
-
1-deoxyaminocyclopentitetrol
-
-
0.4
-
1-deoxymannojirimycin
Q24451
-
0.75
-
1-deoxymannojirimycin
-
pH 5.5, liver lysosomal fraction
0.0028
-
1-phenyl-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
pH 5.75, 25C
-
7.5
-
2-deoxy-2-fluoro-alpha-D-mannosyl fluoride
-
pH 5.6, 37C, D341N mutant GMII
0.6
-
5-fluoro-beta-L-gulosyl fluoride
-
pH 5.6, 37C, D341N mutant GMII
0.02
-
8,8a-di-epi-swainsonine
-
liver lysosomal fraction
0.75
-
8a-epi-swainsonine
-
liver lysosomal fraction
0.4
-
deoxymannojirimycin
Q24451
pH 5.6
0.07
-
gluco-hydroxyiminolactam
Q24451
; pH 5.6
0.013
-
glucoimidazole
Q24451
; pH 5.6
5
-
kifunensine
Q24451
pH 5.6
5.2
-
kifunensine
-
pH 5.75, 37C
0.002
-
mannoimidazole
Q24451
; pH 5.6
0.00021
-
mannostatin
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
3.6e-05
-
Mannostatin A
-
-
3.6e-05
-
Mannostatin A
-
;
0.00015
-
mannostatin B
-
;
0.000249
-
N-benzyl mannostatin A
-
-
0.000249
-
N-benzyl-mannostatin
-
-
0.017
-
N-octyl-6-epi-valienamine
Q24451
; pH 5.6
0.02
-
noeuromycin
Q24451
; pH 5.6
1.05e-05
-
swainsonine
-
pH 5.75, 37C
2e-05
-
swainsonine
Q24451
; pH 5.6
2e-05
-
swainsonine
-
-
0.000155
-
swainsonine
-
-
0.003
-
swainsonine
-
pH 5.75, 25C
0.018
-
swainsonine
Q99YP5
-
0.52
-
[[(3S,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)piperidin-2-ylidene]amino] N-(4-chlorophenyl)carbamate
Q24451
pH 5.6
50
-
meso-aminocyclopentitretrol
-
reaction volume containing 4-methylumbelliferyl alpha-D-mannopyranoside, sodium acetate pH 5.6 and ZnCl at 37C
additional information
-
additional information
-
although too weak for full Ki analyses with the amounts of material available, all analogues with salacinol-like stereochemistry at positions 2 and 3 proved to be weak inhibitors of the enzyme with IC50 values of approximately 7.5 mM
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00025
-
(1S,2R,5R,8R,8aR)-5-[2-(4-tert-butylphenyl)ethyl]octahydroindolizine-1,2,8-triol
-
pH 5.75, 25C
4.4e-05
-
(1S,2R,5S,8R,8aR)-5-[2-(4-tert-butylphenyl)ethyl]octahydroindolizine-1,2,8-triol
-
pH 5.75, 25C
0.8
-
(2R,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
0.72
-
(2R,3R,4S)-2-([[(1S)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
-
1
-
(2R,3R,4S,5R)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-5-methylpyrrolidine-3,4-diol
-
-
0.025
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
extracted from endothelial cells HCEC
0.05
-
(2S,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol
-
extracted from human glioblastoma cells LN18; extracted from human glioblastoma cells LNZ308
0.075
-
(2S,3R,4S)-2-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]pyrrolidine-3,4-diol
-
extracted from endothelial cells HCEC; extracted from human glioblastoma cells LNZ308
0.2
-
(2S,3R,4S)-2-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]pyrrolidine-3,4-diol
-
extracted from human glioblastoma cells LN18
0.0005
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
extracted from endothelial cells HCEC; extracted from human glioblastoma cells LNZ308
0.002
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one
-
extracted from human glioblastoma cells LN18
0.05
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
extracted from human glioblastoma cells LNZ308
0.075
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
extracted from endothelial cells HCEC
0.35
-
(3R,4R,5S)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one
-
extracted from human glioblastoma cells LN18
0.00075
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxy-1-methylpyrrolidin-2-one
-
extracted from endothelial cells HCEC
0.0075
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxy-1-methylpyrrolidin-2-one
-
extracted from human glioblastoma cells LNZ308
0.075
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxy-1-methylpyrrolidin-2-one
-
extracted from human glioblastoma cells LN18
0.075
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxypyrrolidin-2-one
-
extracted from endothelial cells HCEC
0.15
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxypyrrolidin-2-one
-
extracted from human glioblastoma cells LNZ308
0.75
-
(3R,4R,5S)-5-[([(1R)-2-[(4-bromophenyl)(hydroxy)methoxy]-1-phenylethyl]amino)methyl]-3,4-dihydroxypyrrolidin-2-one
-
extracted from human glioblastoma cells LN18
2.5
-
(RS)-2-phenylethyl alpha-D-mannopyranosyl sulfoxide
-
in 50 mM sodium acetate buffer pH 5.8, at 37C
-
2.9e-05
-
1-(4-methylphenyl)-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone, 1-(4-tert-butylphenyl)-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
pH 5.75, 25C
-
0.00025
-
1-(4-tert-butylphenyl)-2-[(1S,2R,5S,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
pH 5.75, 25C
3e-05
-
1-phenyl-2-[(1S,2R,5R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizin-5-yl]ethanone
-
pH 5.75, 25C
-
1.5
-
2-phenylethyl alpha-D-mannopyranosyl sulfone
-
in 50 mM sodium acetate buffer pH 5.8, at 37C
-
0.014
-
8-epi-lentiginosine
-
-
2
-
benzyl alpha-D-mannopyranosyl sulfone
-
in 50 mM sodium acetate buffer pH 5.8, at 37C
-
9e-05
0.0001
D-Mannonolactam amidrazone
-
equally as effective as mannostatin A, IC50: 90-100 nM
0.0004
-
D-Mannonolactam amidrazone
-
IC50: 400 nM
2
-
di-epi-swainsonine
-
-
1e-05
-
Mannostatin A
-
very potent inhibitor, competitive, IC50: about 10 nM with 4-nitrophenyl alpha-D-mannoside as substrate, about 90 nM with GlcNAc(Man)5GlcNAc as substrate, equally potent as swainsonine
0.00013
-
Mannostatin A
-
in 50 mM sodium acetate buffer pH 5.8, at 37C
5e-06
-
swainsonine
-
in 50 mM sodium acetate buffer pH 5.8, at 37C
1e-05
-
swainsonine
-
alpha-mannosidase III, IC50: 10 nM
1e-05
-
swainsonine
-
extracted from endothelial cells HCEC
1.7e-05
-
swainsonine
-
-
2e-05
-
swainsonine
-
extracted from human glioblastoma cells LNZ308
3.7e-05
-
swainsonine
-
pH 5.75, 25C
5e-05
-
swainsonine
-
extracted from human glioblastoma cells LN18
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1.425
-
-
4-nitrophenyl alpha-D-mannoside as substrate
3.1
-
-
pH 5.5, 37C
4.2
-
-
purified recombinant TM1851
5.4
-
-
purified native enzyme
6.38
-
Q9LFR0
purified recombinant GMII expressed in insect cells, substrate 4-nitrophenyl alpha-mannoside
6.75
-
-
intact 124 kDa Man II
7.03
-
-
chymotrypsin-cleaved soluble 110 kDa catalytic subunit
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-, P27046
-
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
-
-
4-nitrophenyl alpha-D-mannoside hydrolysis
5.5
-
-
assay at
5.5
-
-
-
5.5
-
-, P27046
endogenous enzyme in 3T3 cells and recombinant enzyme expressed in COS cells
5.5
-
-
recombinant alpha-mannosidase IIx
5.6
-
-
assay at
5.75
-
-
in MES buffer
5.75
-
-
assay at
5.8
6.4
-
-
5.8
-
-
(Man)8GlcNAc as substrate
5.8
-
Q9LFR0
assay at
6
6.5
-
-
6
-
-
non-reduced GlcNAc(Man)5(GlcNAc)2 hydrolysis
6.5
-
-
-
6.8
-
Q99YP5
assay at
additional information
-
-
neutral pH-optimum
additional information
-
-
optimal pH is between 6.25 and 6.75
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.5
6
-
pH 3.5: more than 70% of maximal activity, pH 6: about half-maximal activity
4.2
6
-
pH 4.2: about half-maximal activity, pH 6: about 80% of maximal activity
4.25
8
-
-
4.8
7
-
about half-maximal activity at pH 4.8 and 7
5.5
6.7
-
alpha-mannosidase III activity is negligible at pH 5.5, increases at pH 5.7-5.9, decreases at pH 6.1 and rises to a plateau at pH 6.5-6.7
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
Q9LFR0
assay at
37
-
-
assay at
37
-
Q99YP5
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
8.5
-
low activity at neutral pH
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.3
-
-
for the first isoform of the enzyme, isoelectric focusing
4.6
-
-
method not mentioned
4.8
-
-
for the second isoform of the enzyme, isoelectric focusing
5.8
-
-
pH 3 to 10 gradient, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
clear cells in all epdididymal regions, not in principal cells
Manually annotated by BRENDA team
-
mutant HEK293T cell line called Lec36, which displays sensitivity to ricin that lies between the parental HEK 293T cells, in which the secreted and membrane-expressed proteins are dominated by complex-type glycosylation, and 293S Lec1 cells, which produce only oligomannose-type N-linked glycans. Lec36 cells are dominated by hybrid-type glycosylation. Wild-type and mutant enzyme expression analysis, overview
Manually annotated by BRENDA team
-
alpha-mannosidase IIx
Manually annotated by BRENDA team
-
in the Golgi apparatus
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
freeze-dried mixture of mycelium and its culture medium, commercially available as Morushin
Manually annotated by BRENDA team
-
BALB/clone A31
Manually annotated by BRENDA team
-
normal kidney cells
Manually annotated by BRENDA team
-
in the Golgi apparatus
Manually annotated by BRENDA team
-
baculovirus-infected IPLB-SF-21AE cells
Manually annotated by BRENDA team
-
in the Golgi apparatus of Sertoli and Leydig cells
Manually annotated by BRENDA team
additional information
-
tissue distribution of Man II mRNA
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
hepatocytes cultured in dexamethason-supplemented medium
Manually annotated by BRENDA team
-
granularly distributed
Manually annotated by BRENDA team
-
at least 3 forms of alpha-mannosidase III, the smallest form accumulates in the extracellular fraction
-
Manually annotated by BRENDA team
-
Golgi alpha-mannosidase II
Manually annotated by BRENDA team
Q9LFR0
Golgi alpha-mannosidase II, the enzyme has a transmembrane domain and a cytoplasmic tail sufficient for localisation of the enzyme to the Golgi complex, retention by lumenal sequences is not involved, retention mechanism
Manually annotated by BRENDA team
-
integral membrane protein, hydrophilic catalytic domain is anchored to the lumenal face of Golgi membranes through an NH2-terminal hydrophobic membrane-anchoring domain
Manually annotated by BRENDA team
-
topology study: integral membrane protein with lumenal orientation, hydrophilic catalytic domain is bound to an integral hydrophobic membrane anchoring domain through a proteolytically sensitive linkage
Manually annotated by BRENDA team
-, P27046
type II transmembrane protein with short cytoplasmic tail, single transmembrane domain and large C-terminal catalytic domain
Manually annotated by BRENDA team
-
type II transmembrane enzyme, subcompartmental localization, mainly over medial saccules of the Golgi stack
Manually annotated by BRENDA team
-
type II membrane protein, alpha-mannosidase II and IIx
Manually annotated by BRENDA team
-
alpha-mannosidase III, integral membrane glycoprotein with type II topology
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
Q99YP5
SpGH38 may be intracellular, absence of any classical signal peptide
Manually annotated by BRENDA team
-
type II transmembrane protein with short cytoplasmic tail, single transmembrane domain and large hydrophilic C-terminal domain
Manually annotated by BRENDA team
-
membrane-bound, predominantly in the microsomal pellet
Manually annotated by BRENDA team
Q9LFR0
Golgi alpha-mannosidase II is a type II membrane protein
Manually annotated by BRENDA team
Bombyx mori Bm-N
-
membrane-bound, predominantly in the microsomal pellet
-
Manually annotated by BRENDA team
-
predominantly, membrane-bound
-
Manually annotated by BRENDA team
-
hepatocytes cultured in colchicine-containing medium
Manually annotated by BRENDA team
Bombyx mori Bm-N
-
predominantly, membrane-bound
-
-
Manually annotated by BRENDA team
additional information
-
absent from the endoplasmic reticulum, lysosomes, and autophagosomes
-
Manually annotated by BRENDA team
additional information
-, Q5I5K3
AfAms1 contains no cleavable signal sequence or transmembrane domain
-
Manually annotated by BRENDA team
additional information
Aspergillus fumigatus YJ-407
-
AfAms1 contains no cleavable signal sequence or transmembrane domain
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
74000
-
-
SDS-PAGE
81000
-
-
native-PAGE
97000
-
-
SDS-PAGE
110000
-
-
sucrose density gradient centrifugation
110000
-
-
native-PAGE
230000
-
-
chymotrypsin-cleaved 110 kDa catalytic subunit, gel filtration
240000
-
-
PAGE under nonreducing conditions
285000
-
-
intact enzyme, gel filtration
295000
-
-
tetrameric form, gel filtration
340000
-
-
gel filtration
468000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 128000, SDS-PAGE
?
-
x * 110000 + x * 14000, 110 kDa proteolytically resistant, hydrophilic catalytic domain and 14 kDa hydrophobic membrane anchoring domain, generated by mild chymotrypsin digest, SDS-PAGE; x * 124000, intact subunit, SDS-PAGE
?
-
x * 134000-136000, MW after posttranslational modification, initial synthesis product of 124 kDa, SDS-PAGE
?
-
x * 124000, intact subunit, SDS-PAGE
?
-
x * 125000, SDS-PAGE
?
-, P27046
x * 131000, predicted from the amino acid sequence
?
-
x * 127000, predicted from the amino acid sequence
?
-
x * 120500, D341N mutant GMII
?
-
x * 150000, intact glutathione S-transferase-tagged secreted form of SfManIII, SDS-PAGE
?
-
x * 120000, SDS-PAGE
?
-, Q5I5K3
x * 124000
?
Aspergillus fumigatus YJ-407
-
x * 124000
-
dimer
-
2 * 110000, chymotrypsin-cleaved catalytic subunit, SDS-PAGE; 2 * 124000, intact enzyme, SDS-PAGE; disulfide-linked homodimer
dimer
-
2 * 128000, SDS-PAGE; disulfide-linked homodimer
tetramer
-
4 * 75000-80000, enzyme exists also in a relatively stable 150 kDa dimeric form, SDS-PAGE
tetramer
-
4 * 112000, SDS-PAGE
trimer
-
3 * 120000, SDS-PAGE
dimer
-
2 * 120000, SDS-PAGE; disulfide-linked homodimer
additional information
Q9LFR0
the enzyme has a transmembrane domain and a cytoplasmic tail sufficient for localisation of the enzyme to the Golgi complex, retention by lumenal sequences is not involved
additional information
Q99YP5
structure comparisons, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
Q9LFR0
recombinant secreted His-tagged soluble enzyme from culture medium of Spodoptera frugiperda Sf21 insect cells is N-glycosylated ans sensitive to PNGaseF
glycoprotein
-
N-glycosylation, the sugar chain of the enzyme is recognized by concanavalin A, no digestion by endoglycosidase H, glycan type is deduced as GlcNAc2Man3Xyl1Fuc1GlcNAc2, bianntenary plant complex type N-glycans
glycoprotein
-
addition of O- and asparagine-linked oligosaccharides
phosphoprotein
-
phosphate is present as serine phosphate
glycoprotein
-
addition of asparagine-linked oligosaccharides, not O-glycosylated
glycoprotein
-, P27046
-
phosphoprotein
-
-
glycoprotein
-
presumably
glycoprotein
-
alpha-mannosidase III is initially synthesized as a high-mannose glycoprotein precursor, its N-glycans are trimmed as it is transported to the Golgi apparatus, N-glycosylation is required for the production of active enzyme
proteolytic modification
-
a subpopulation of Golgi alpha-mannosidase III appears to be proteolytically cleaved and is secreted in enzymically active form
glycoprotein
-
presumably an N-linked glycoprotein with high-mannose chains
glycoprotein
-
-
additional information
-
study of posttanslational modifications, sulfate is attached to N-linked oligosaccharide, no proteolytic modification
lipoprotein
-
[3H]palmitate can be incorporated into enzyme, glycosylation is not required for fatty acid attachment
additional information
-
study of posttanslational modifications, sulfate is attached to N-linked oligosaccharide, no proteolytic modification
glycoprotein
-
integral membrane glycoprotein
additional information
-
study of biosynthesis and processing of alpha-mannosidase III
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
; in complex with inhibitor mannostatin A and its derivatives. The interaction with the backbone carbonyl of residue R876 is crucial to the high potency of the inhibitor and enhanced by the hydrophobic interaction between the thiomethyl group and an aromatic pocket vivinal to the cleavage site
-
; in complex with inhibitors (3R,4R,5R)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidin-2-one and (3R,4R,5R)-3,4-dihydroxy-5-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-1-methylpyrrolidin-2-one, to 1.08 A and 1.74 A resolution, respectively
-
; in complex with inhibitors mannoimidazole, glucoimidazole, N-octyl-6-epi-valienamine, gluco-hydroxyiminolactam, and [[(3S,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)piperidin-2-ylidene]amino] N-(4-chlorophenyl)carbamate
Q24451
; mutants D204A and D341N in complex with 2,4-dinitrophenyl-alpha-D-mannopyranoside and in complex with oligosaccharides containing an alpha-(1,6)-or alpha-(1,3)-linked 1-thio-alpha-mannoside
-
by hanging-drop vapor diffusion method, GMII in complex with inhibitors di-epi-swainsonine and 8-epi-lentiginosine, both adopt a 3C6/E7 conformation, water molecule substructure in the active site plays a significant role in dictating inhibitory activity
-
crystal structure of enzyme with bound inhibitors kifunensine, swainsonine and 1-deoxymannojirimycin
-
enzyme in complex with inhibitors mannostatin A, N-benzyl mannostatin A, and 1-deoxyaminocyclopentitetrol, crystal growth overnight of enzyme solved in phosphate buffered reservoir solution, crystals are soaked for 3-6 h in 10 mM ligand solution, co-crystallization in Tris buffer without phosphate washing, X-ray diffraction structure determination and analysis, molecular modelling and structure simulation, overview
-
enzyme with bound unhibitors, X-ray diffraction structure determination and analysis
-
GMII complexed with inhibitors (2R,3R,4S)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol, (2R,3R,4S)-2-([[(1S)-2-hydroxy-1-phenylethyl]amino]methyl)pyrrolidine-3,4-diol, and (2R,3R,4S,5R)-2-([[(1R)-2-hydroxy-1-phenylethyl]amino]methyl)-5-methylpyrrolidine-3,4-diol, to 1.30-1.45 A resolution
-
hanging drop vapor diffusion
-
in complex with natural substrate GlcNAcMan5GlcNAc2 and with oligosaccharide Man5. The natural substrate binds in a large groove on the surface of the enzyme. This groove contains the site of the nucleophile D204, acid/base catalyst D341, and zinc ion. substrate binding does not induce any noticeable conformational change. the larger active site cleft contains three sugar-binding subsites
-
wild-type and D341N mutant GMII, hanging drop vapor diffusion
-
purified recombinent enzyme free or in complex with the inhibitor swainsonine, sitting drop vapour diffusion method, mixing of 12 mg/ml protein in 100 mM Tris, pH 8.5, 1.5 M (NH4)2SO4 and 12% v/v glycerol, with reservoir solution, containing 3% v/v glycerol, 54% v/v Tacsimate, pH 7.0, and 2% v/v PEG 6000, also acting as the cryo-protectant, crystals of the swainsonine complex form are obtained by soaking SpGH38 crystals for ,16 h in mother liquor supplemented with 2 mM swainsonine, X-ray diffraction structure determination and analysis at 1.9 A and 2.6 A resolution, respectively
Q99YP5
purified recombinant TM1851, sitting drop vapour diffusion method, optimal conditions: 0.001 ml of protein solution containing 5.3 mg/ml protein in 5 mM sodium phosphate and 150 mM NaCl, pH 6.8, mixed with an equal volume of reservoir solution containing 4% w/v PEG 6000, 50 mM sodium phosphate, pH 6.0, and 0.5 M NaCl, 1 day at 25C, X-ray diffraction structure determination and preliminary analysis at 2.9 A resolution
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
6
-
unstable at 37C, no activity below pH 4
4
-
-
1 h, at 37C, inactivation, 1 mM ZnCl2 partially stabilizes
5
7
-
the enzyme is most stable, inactivation below pH 5.0 and above pH 8.0 is irreversible
6
-
-
1 h, at 37C, 30% loss of activity
6
-
-
below, high loss of activity within 1 week
6.5
-
-
below, loss of activity
7
9
-
stable at 37C
8
-
-
1 h, at 37C, stable
additional information
-
-
pH dependent denaturation, kinetics, overview
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
90
-
activity is reduced by 8% at 50C while positive ellipticity at 190-195 nm is almost same in the temperature range of 35-50C. The activity is not affected in this range. At 60C, 18% and at 70C and above, 25% loss in the alpha-helical content of the protein occurs with significant decrease in the positive ellipticity, the protein does not completely unfold at 90C
37
-
-
24 h, in 100 mM sodium acetate buffer, pH 5.8, 30-50% loss of activity
37
-
-
stable at pH 7-9, unstable at acidic pH-values, Zn2+ stabilizes
40
-
-
and below, 15 min stable, rapid inactivation above, Zn2+ or 0.125 mg/l bovine serum albumin stabilizes
50
-
-
3 h, about 30% loss of activity, 4-nitrophenyl alpha-D-mannoside or (Man)9GlcNAc as substrate
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
unfolding and denaturation in 6 M guanidinium hydrochloride, the protein almost completely unfolds in 4.0 M guanidinium hydrochloride, overview
-
4-nitrophenyl alpha-D-mannoside stabilizes
-
enzyme retains full activity after incubation with chymotrypsin or other proteases that cleave the enzyme into catalytic and membrane-anchoring domains, a decrease in activity occurs with a corresponding cleavage of the catalytic subunit to a MW 105000 species
-
freezing and thawing greatly enhances the rate of cleavage of the intact enzyme
-
requires presence of detergent, 0.1% Triton X-100, to maintain enzyme in soluble form
-
stable to repeated freeze-thawing cycles
-
ultrafiltration, even in the presence of PMSF at 0C, results in a slow conversion of the intact enzyme to the 110 kDa degradation product, the catalytic domain, which itself is extremely stable
-
freezing inactivates column-bound glutathione S-transferase-tagged secreted form of SfManIII
-
glycerol stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C or 4C, 10 mM sodium acetate buffer, pH 5, with or without CaCl2, 4 months, stable
-
-20C or 4C, 4 months, less than 5% loss of activity
-
2-4C, 10 mM potassium phosphate buffer, pH 7.2, 1% Triton X-100, 4 weeks, 20% loss of activity
-
4C, intact enzyme, several weeks, stable
-
5C or frozen, 0.1 M potassium phosphate buffer, pH 7.2, Triton X-100, 30 days, 20% loss of activity
-
frozen, at least 2 months, stable
-
4C, column-bound glutathione S-transferase-tagged secreted form of SfManIII, at least 1 week, stable
-
0-4C, 10 mM HEPES buffer, pH 7.1, 0.1% Triton X-100, 0.5 mM PMSF, 0.2 mM dithiothreitol, 10% glycerol, at least 2 weeks, stable
-
0-4C, 10 mM HEPES buffer, pH 7.2, 10% glycerol, several days, stable
-
frozen, 10 mM HEPES buffer, pH 7.1, 0.1% Triton X-100, 0.5 mM PMSF, 0.2 mM dithiothreitol, 10% glycerol, at least 2 months, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant secreted His-tagged soluble enzyme from culture medium of Spodoptera frugiperda Sf21 insect cells by nickel affinity chromatography
Q9LFR0
anion-exchange chromatography, chromatofocusing chromatography, gel filtration
-
method not mentioned
-
native enzyme 600fold from mature seeds to homogeneity by ammonium sulfate fractionation, ion exchange and hydrophobic interaction chromatography, and gel filtration, and another 2 steps of ion exchange chromatography and gel filtration
-
native enzyme from mature seeds to homogeneity by ammonium sulfate fractionation, ion exchange and hydrophobic interaction chromatography, and gel filtration
-
ammonium sulfate fractionation of recombinant enzyme followed by two cobalt chelating chromatography steps
-
partial
-
recombinant protein A fusion of alpha-mannosidase II and IIx, expressed in COS cells
-
soluble alpha-mannosidase IIx protein purified by a nickel affinity column
-
intact 124 kDa Man II and chymotrypsin-cleaved soluble 110 kDa catalytic subunit
-
glutathione S-transferase-tagged secreted form of SfManIII
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
Q99YP5
recombinant TM1851 from Escherichia coli by ion exchange and hydroxyapatite chromatography, and gel filtration
-
1200fold
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
GMII, DNA and amino acid sequence determination and analysis, expression of His-tagged functional Golgi alpha-mannosidase II as soluble protein, which is secreted to the culture medium, in Spodoptera frugiperda Sf21 insect cells using the baculovirus transfection system, transient expression of GFP-tagged enzyme in Nicotiana benthamiana plants shows localization of the recombinant enzyme to the Golgi and endoplasmic reticulum
Q9LFR0
DNA and amino acid sequence determination and analysis
-, Q5I5K3
GmII is cloned, sequenced and localized to a single site, 85D14-18, on the right arm of chromosome 3
-
alpha-mannosidase II and IIx, expression in COS cells as protein A fusion, overexpression of alpha-mannosidase IIx in CHO-K1 cells
-
expressed in Drosophila melanogaster
-
expressed in HEK293 cells
-
gene MAN2A1 from mutant strain Lec36 and wild-type gene, DNA and amino acid sequence determination and analysis. Wild-type and mutant enzyme expression analysis, overview
-
Golgi mannosidase II gene is located on chromosome 5q21, Golgi mannosidase IIx on chromosome 15q25
-
isolation of partial cDNA clones, gene is located on chromosome 5
-
preparation of expression construct containing 6 x His and tobacco etch virus protease recognition sites in the N-terminus of NAM and integrated into the Pichia pastoris chromosome under inducible alcohol oxygenase promoter. CHO-K1 cells transfected with pNAM-EGFP
-
cDNA fragments encoding full-length enzymes subcloned into the pcDNA3.1 mammalian expression vector. cDNA fragments encoding soluble forms of enzymes subcloned into pcDNA-HSH. Full-length alpha-mannosidase IIx expressed in MII/alpha-mannosidase IIx double-null fibroblasts. Soluble recombinant alpha-mannosidase IIx expressed in COS cells
-
full-length cDNA is cloned and sequenced, 8-12fold overexpression in COS cells
-, P27046
pcDNA-HSH-MX expression vector encoding the soluble alpha-mannosidase IIx, transfection into Cos-1 cells
-
alpha-mannosidase III cDNA is cloned
-
gene M1 GAS SF370, DNA and amino acid sequence determination and analysis, cloning of the coding sequence for SpGH38 residues 1-901, overexpression as 3C protease cleavable N-terminal His6-tagged enzyme in Escherichia coli strain BL21(DE3)
Q99YP5
TM1851, expression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D204A
-
almost complete loss of activity. Residue D204 is involved in the conformational change of the bound mannoside to a high-energy B2,5 conformation. In the mutant, mannose adopts the low-energy 4C1 conformation; mutant of Drosophila melanogaster, residual mannosidase activity
D341N
-
mutant with removed acid/base catalyst, 2fold lower Km and 200fold kcat values compared with the wild-type enzyme
R60Q/R73N/L79S/E81S
-
beta1,4-N-acetylglucosaminyltransferase III-ManII mutant with amino acid substitutions in the localization domain of ManII, is expressed in similar amounts as beta1,4-N-acetylglucosaminyltransferase III-ManII, yields antibody glycovariants featuring substantially reduced proportions of bisected non-fucosylated oligosaccharides compared to the non-mutated beta1,4-N-acetylglucosaminyltransferase III-ManII
additional information
Q9LFR0
construction of two Golgi alpha-mannosidase II knockout mutant plants, lines Salk_052443 and Salk_141821, resulting in predominant presence of unprocessed N-glycans but revealing also that alternative routes for N-glycan processing exist in the plants, mutant substrate specificity analysis, overview
additional information
-, Q5I5K3
construction of a knockout mutant DELTAAfams1, deletion of the Afams1 leads to a severe defect in conidial formation, especially at a higher temperature. In addition, abnormalities of polarity and septation are associated with the DELTAAfams1 mutant, phenotype and morphogenesis of the DELTAAfams1 mutant, detailed overview. Construction of a complemented strain by reintroduction of a wild-type copy of Afams1 directly into the mutated locus, under the control of its own promoter
additional information
Aspergillus fumigatus YJ-407
-
construction of a knockout mutant DELTAAfams1, deletion of the Afams1 leads to a severe defect in conidial formation, especially at a higher temperature. In addition, abnormalities of polarity and septation are associated with the DELTAAfams1 mutant, phenotype and morphogenesis of the DELTAAfams1 mutant, detailed overview. Construction of a complemented strain by reintroduction of a wild-type copy of Afams1 directly into the mutated locus, under the control of its own promoter
-
D341N
-
acid-base mutant, residual mannosidase activity; almost complete loss of activity. Substrate mannose is found in a distorted high energy B2,5 conformation, which is necessary for it to fit in the confined space of the binding pocket
additional information
-
the mutant gene MAN2A1 from strain Lec36 harbors a point mutation in the active site in one allele and an in-frame deletion of 12 nucleotides in the other allele, compared to parent HEK293T cells, which alters the glycosylation pattern. Expression of the wild-type but not the mutant MAN2A1 alleles in Lec36 cells restores processing of the 19A reporter glycoprotein to complex-type glycosylation, overview
R73N/L79S/E81S
-
beta1,4-N-acetylglucosaminyltransferase III-ManII mutant with amino acid substitutions in the localization domain of ManII, is expressed in similar amounts as beta1,4-N-acetylglucosaminyltransferase III-ManII, yields antibody glycovariants featuring substantially reduced proportions of bisected non-fucosylated oligosaccharides compared to the non-mutated beta1,4-N-acetylglucosaminyltransferase III-ManII
additional information
-
mutants without GlcNAc(Man)5(GlcNAc)2 activity, Golgi mannosidase II-null mice phenotype
additional information
-
MII/alpha-mannosidase IIx double knockout mice synthesize no complex-type N-glycans
additional information
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MII/alpha-mannosidase IIx double knockout mice, completely lack complex-type N-glycans, some double-nulls die between embryonic days 15.5 and 18.5, but most survive until shortly after birth and die of respiratory failure. Alpha-mannosidase IIx-null mice are mainly complex-type and also contain high-mannose-type but not significant levels of hybrid-type N-glycans. In contrast, MII-null embryos show high levels of hybrid-type N-glycans and reduced levels of complex-type N-glycans
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
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development of specific inhibitors of GMII that can lead to novel anti-metastatic or anti-inflammatory compounds
drug development
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the enzyme Golgi alpha-mannosidase II is a promising target for intervention in the glycosylation process
medicine
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promising target for drug development in anti-tumor therapies, ability of seven available docking programs to predict the binding mode and binding affinity of alpha-mannosidase II inhibitors
biotechnology
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the Lec36 cell line will be useful for expressing therapeutic glycoproteins with hybrid-type glycans and as a sensitive host for detecting mutations in human MAN2A1 causing type II congenital dyserythropoietic anemia
medicine
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reduced expression of Man II in the autosomal genetic HEMPAS disease, i.e. hereditary erythroblastic multinuclearity associated with positive acidified serum
medicine
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enzyme deficiency causes congenital dyserythropoietic anemia with splenomegaly and various additional abnormalities and complications; reduced expression of Man II in the autosomal genetic HEMPAS disease, i.e. hereditary erythroblastic multinuclearity associated with positive acidified serum
medicine
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enzyme deficiency causes congenital dyserythropoietic anemia with splenomegaly and various additional abnormalities and complications
medicine
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alpha-mannosidase IIx is an isozyme of MII. Either MII or alpha-mannosidase IIx can biochemically compensate for the deficiency of the other in vivo, and either of two is required for late embryonic and early postnatal development