Information on EC 2.4.1.83 - dolichyl-phosphate beta-D-mannosyltransferase

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

EC NUMBER
COMMENTARY hide
2.4.1.83
-
RECOMMENDED NAME
GeneOntology No.
dolichyl-phosphate beta-D-mannosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GDP-alpha-D-mannose + dolichyl phosphate = GDP + dolichyl beta-D-mannosyl phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
dolichyl-diphosphooligosaccharide biosynthesis
-
-
Metabolic pathways
-
-
N-Glycan biosynthesis
-
-
protein N-glycosylation (eukaryotic, high mannose)
-
-
protein N-glycosylation (Haloferax volcanii)
-
-
SYSTEMATIC NAME
IUBMB Comments
GDP-mannose:dolichyl-phosphate beta-D-mannosyltransferase
Acts only on long-chain polyprenyl phosphates and alpha-dihydropolyprenyl phosphates that are larger than C35.
CAS REGISTRY NUMBER
COMMENTARY hide
62213-44-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ecotype Columbia
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Haloferax volcanii WR536 (H53)
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
synthetic construct
-
-
-
Manually annotated by BRENDA team
QM 9414
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
L. inbred A636
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
loss-of-function mutations and RNA interference-mediated reduction of DPMS1 expression in Arabidopsis causes a wrinkled seed coat phenotype and most remarkably enhanced hypersensitivity to ammonium that is manifested by extensive chlorosis and a strong reduction of root growth
metabolism
-
dolichyl phosphate mannose synthase is a key enzyme in the O-glycosylation pathway
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6Z,10E,14E,18E,22E)-3,7,15,19,23,27-hexamethyl-11-[(naphthalen-1-ylamino)methyl]octacosa-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate + dolichyl phosphate
?
show the reaction diagram
-
-
-
-
?
(6Z,10Z,14Z,18Z,22E,26E)-3,7,11,15,19,23,27-heptamethyl-30-(naphthalen-1-ylamino)triaconta-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate + dolichyl phosphate
?
show the reaction diagram
-
-
-
-
?
(6Z,10Z,14Z,18Z,22Z,26Z,30E,34E,38E)-3,7,11,15,19,23,27,31,35,39-decamethyl-42-(naphthalen-1-ylamino)dotetraconta-6,10,14,18,22,26,30,34,38-nonaen-1-yl dihydrogen phosphate + dolichyl phosphate
?
show the reaction diagram
-
-
-
-
?
GDP-mannose + C110-dolichyl phosphate
GDP + C110-dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + C120-dolichyl phosphate
GDP + C120-dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + C55-undecaprenyl phosphate
GDP + C55-undecaprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + C85-dolichyl phosphate
GDP + C85-dolichyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
GDPmannose + (S)-3-methyloctadecanyl phosphate
GDP + (S)-3-methyloctadecanyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + C100 alpha-dihydropolyprenyl phosphate
GDP + C100 alpha-dihydropolyprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + C55 alpha-dihydropolyprenyl phosphate
GDP + C55 alpha-dihydropolyprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + C55-polyisoprenol
GDP + D-mannosyl-C55-polyisopropenol
show the reaction diagram
-
-
-
-
?
GDPmannose + C80 alpha-dihydropolyprenyl phosphate
GDP + C80 alpha-dihydropolyprenyl D-mannosyl phosphate
show the reaction diagram
-
-
-
-
?
GDPmannose + cetyl phosphate
GDP + cetyl D-mannosyl phosphate
show the reaction diagram
-
less efficient than dolichol phosphate
-
-
?
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
GDPmannose + farnesyl phosphate
GDP + farnesyl D-mannosyl phosphate
show the reaction diagram
-
less efficient than dolichol phosphate
-
-
?
GDPmannose + phytanyl phosphate
GDP + phytanyl D-mannosyl phosphate
show the reaction diagram
-
at 60-70% of the activity with dolichyl phosphate
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GDP-mannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
GDPmannose + dolichyl phosphate
GDP + dolichyl D-mannosyl phosphate
show the reaction diagram
additional information
?
-
-
increased availability of GDP-mannose corrects glycosylation defects in the endoplasmic reticulum, such as dolichyl D-mannosyl phosphate formation in dolichyl-phosphate beta-D-mannosyltransferase mutants of Saccharomyces cerevisiae
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-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoic acid)
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-
Amphomycin
GDP-2-deoxy-D-glucose
-
-
GDP-3-deoxy-D-mannose
-
-
GDP-4-deoxy-D-mannose
-
-
GDP-6-deoxy-D-mannose
-
-
GDP-D-glucose
-
0.01 mM, 50% inhibition
lucifer yellow iodoacetamide
-
-
Nonidet P-40
-
0.01%, 50% inhibition
p-hydroxymercuribenzoate
phosphatidylinositol
-
relative activity: 70%
tunicamycin
-
-
[(5Z)-4-oxo-5-(phenylmethylidene)-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
42% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
23% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates
[(5Z)-5-[(3-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
90% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-chlorophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
86% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-cyanophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
73% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-ethynylphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
94% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[(4-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
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70% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates
[(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
20% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates
[(5Z)-5-[[3-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
23% residual DPMS activity in the presence of 1 mM
[(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
10% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8-bromo-cAMP
-
capillary endothelial cells treated with the cAMP enhancer 8-bromo-cAMP show a 20% and 30% higher activity after 24h and 32h, respectively
lysophosphatidylcholine
-
activates
phosphatidylcholine
phosphatidylethanolamine
phosphatidylglycerol
-
relative activity: 356%
phosphatidylinositol
phosphatidylserine
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relative activity: 342%
Phospholipid
-
no absolute requirement for phospholipid, the phospholipid is required for interaction of the enzyme with the long chain polyisoprenol substrate dolichyl phosphate
sphingomyelin
-
activates
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0751
(6Z,10E,14E,18E,22E)-3,7,15,19,23,27-hexamethyl-11-[(naphthalen-1-ylamino)methyl]octacosa-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate
-
pH 7.5
0.0246
(6Z,10Z,14Z,18Z,22E,26E)-3,7,11,15,19,23,27-heptamethyl-30-(naphthalen-1-ylamino)triaconta-6,10,14,18,22,26-hexaen-1-yl dihydrogen phosphate
-
pH 7.5
0.0248
(6Z,10Z,14Z,18Z,22Z,26Z,30E,34E,38E)-3,7,11,15,19,23,27,31,35,39-decamethyl-42-(naphthalen-1-ylamino)dotetraconta-6,10,14,18,22,26,30,34,38-nonaen-1-yl dihydrogen phosphate
-
pH 7.5
0.00059
C110-dolichyl phosphate
-
-
0.00159
C120-dolichyl phosphate
-
-
0.00117
C55-undecaprenyl phosphate
-
-
0.0023
C85-dolichyl phosphate
-
-
0.0003 - 0.0143
dolichyl phosphate
0.00018 - 0.0012
GDP-mannose
0.00025 - 0.007
GDPmannose
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000023 - 70.9
GDP-mannose
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.018 - 0.056
GDP
0.0013
GDP-2-deoxy-D-glucose
-
-
0.001
GDP-3-deoxy-D-mannose
-
-
0.0031
GDP-4-deoxy-D-mannose
-
-
0.0004
GDP-6-deoxy-D-mannose
-
-
0.235
GMP
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-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000285
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-
0.0016
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.1
-
Mes buffer or sodium/potassium phosphate buffer
7.5 - 9.5
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-
7.5 - 8
-
potassium phosphate or Tris-HCl buffer
8.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.8 - 8
-
pH 5.8: about 35% of maximal activity, pH 8.0: about 60% of maximal activity
6.5 - 8.5
-
pH 6.5: about 80% of maximal activity, pH 8.5: about 54% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 - 35
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15C: about 60% of maximal activity, 35C: about 30% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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capillary endothelial cell
Manually annotated by BRENDA team
-
higher level of expression in mature female worms, as compared to immature and male worms
Manually annotated by BRENDA team
-
Lec15.1 cell have a single point mutation within the coding region of DPM2 gene. The cDNA of the mutant DPM2 subunit is expressed at a drastically reduced amount of DPM2 protein
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by the small membrane protein DPM3
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
41010
-
deduced from cDNA
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
additional information
-
no glycosylation
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
20 min, complete inactivation, in presence of mitochondrial extract 40% loss of activity, stable for 30 min in presence of sphingomyelin and dolichyl phosphate
40
-
20 min, 50% loss of activity in presence of sphingomyelin and dolichyl phosphate
75
-
protein shows thermostability up to 75C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
in combination dolichyl phosphate and phospholipids are effective in stabilization
-
reducing agents positively influence stability
-
the enzyme is resistant to inactivation by incubation with trypsin unless Triton is present
-
unstable in presence of detergent
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, loss of a third of the activity after 2 weeks
-
-20C, phosphate buffer, pH 6.0, 20 mM Mg2+, 0.2% polidocanol, 20% glycerol, stable for 2 weeks
-
-40C, stable for about a month with 20% loss of activity
-
-70C, 2 weeks, no loss of activity
-
0C, 3 days, 50% loss of activity
-
4C, enzyme is relatively stable when stored overnight in phosphate buffer and retains full activity when stored within liposomes
-
4C, stable for more than 24 h
-
during solubilization the enzyme is stabilized by the presence of lipophilic substrate dilochylphosphate and phospholipids as well as by protease inhibitors
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DEAE-cellulose column chromatography, gel filtration
-
His-tag fusion protein purified using ProBond purification system, more than 97% pure
-
one-step purification
-
solubilized with Triton X-100 and purified to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
capillary endothelial cell clone overexpressing the gene encoding DPMS
synthetic construct
-
cDNA fragments containing the start and stop codons amplified and subcloned into the EcoRV site of the pBluescript II SK(-) cloning vector
-
DPM1 cDNA from wild-type and Lec15.1 cells is identical
-
DPMS (KB-3) gene cloned into the pcDNA3.1/His A vector at the KpnI and XhoI site and transformed into DH5alpha cells. Cloned into Xho I and BamH I sites of pEGFP-N1 to obtain pEGFP-N1-DPMS overexpression plasmid. Transfection of capillary endothelial cells with pEGFP-N1-DPMS overexpression plasmid and pEGFP-N1 vector
-
expressed in Escherichia coli
-
expressed in Trichoderma atroviride strain P1
-
full-length DPMS expressed in Escherichia coli
-
full-length protein is expressed in Escherichia coli and the N-terminal domain is expressed in Saccharomyces cerevisiae
-
functionally active mutant enzyme S141A is expressed in Escherichia coli
functionally expressed in yeast strain DPM 1-6 and Escherichia coli
-
gene can complement a lethal null mutation in Schizosaccharomyces pombe
glycoprotein hypersecretion alters the cell wall in Trichoderma reesei strains expressing the Saccharomyces cerevisiae dolichylphosphate mannose synthase gene
-
the cDNA is amplified in mature males and females
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
capillary endothelial cells harboring DPMS overexpressing plasmid express DPMS higher than pEGFP-N1 vector and the parental cells
-
compared with the mock line, the temporary PEC(Z)/PB lines show a decreased mRNA expression for D-P-M and a clear destruction of porcine endogenous retrovirus infectivity to human cells in the Lac Z pseudotype assay. Compared with parental and mock cells, all PEC(Z)/PB cells transfected with siRNA show a decreased mRNA expression for the D-P-M by one-fifth
-
the DPMS-overexpressing clone has a high level of DPMS mRNA, expresses nearly 4times more DPMS protein than the clone transfected with pEGFP-N1 vector only and has 108% higher DPMS activity than the vector control
synthetic construct
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G10E
-
Lec15.1 cell have a single point mutation within the coding region of DPM2 gene. The mutant DPM2 cDNA is expresses a drastically reduced amount of DPM2 protein
D38A
-
5.8% of the activity of wild-type
D39A
-
2% of the activity of wild-type
D89A
-
0.09% of the activity of wild-type
D91A
-
0.17% of the activity of wild-type
C172S
-
specific activity similar to the wild-type enzyme
C259S
-
specific activity similar to the wild-type enzyme
C93S
-
specific activity similar to the wild-type enzyme
I253N
-
higher value for the apparent Km-value for dolichyl phosphate when assayed in detergent solution, mutation has no effect on Km-value when the enzyme is reconstituted with phosphatidylethanolamine
S141A
functionally active mutant enzyme with more than 50% reduction in catalytic activity compared to wild-type enzyme
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
inhibition of DPMS is a promising strategy for the development of anti-trypanosomal agents. Thiazolidinones [(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid, [(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid and [(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid in particular are promising candidates for further development because of their respective activities against trypanosomal DPMS and GPI anchor biosynthesis
medicine
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