Information on EC 1.1.1.95 - phosphoglycerate dehydrogenase

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

EC NUMBER
COMMENTARY
1.1.1.95
-
RECOMMENDED NAME
GeneOntology No.
phosphoglycerate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-phospho-D-glycerate + NAD+ = 3-phosphonooxypyruvate + NADH + H+
show the reaction diagram
member of the 2-hydroxyacid dehydrogenases family, whereof only the enzymes from E. coli and Pisum sativum utilize phosphorylated substrates and transfer the hydride ion to the A-site of NAD+, uses also alpha-ketoglutarate as substrate
-
3-phospho-D-glycerate + NAD+ = 3-phosphonooxypyruvate + NADH + H+
show the reaction diagram
regulation model with effector L-serine, member of the D-2-hydroxyacid dehydrogenases, D-isomer substrate specific, overview of related enzymes from other species
-
3-phospho-D-glycerate + NAD+ = 3-phosphonooxypyruvate + NADH + H+
show the reaction diagram
model for catalytic mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
-
-
Glycine, serine and threonine metabolism
-
-
L-serine biosynthesis
-
-
Metabolic pathways
-
-
Methane metabolism
-
-
Microbial metabolism in diverse environments
-
-
serine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
3-phospho-D-glycerate:NAD+ 2-oxidoreductase
This enzyme catalyses the first committed step in the phosphoserine pathway of serine biosynthesis in Escherichia coli [2,3]. Reaction (1) occurs predominantly in the reverse direction and is inhibited by serine and glycine. The enzyme is unusual in that it also acts as a D- and L-2-hydroxyglutarate dehydrogenase (with the D-form being the better substrate) and as a 2-oxoglutarate reductase [3]. It has been postulated [3] that the cellular 2-oxoglutarate concentration may regulate serine biosynthesis and one-carbon metabolism directly by modulating the activity of this enzyme.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3-PGDH
-
-
-
-
3-phosphoglycerate dehydrogenase
-
-
-
-
3-phosphoglyceric acid dehydrogenase
-
-
-
-
A10
-
-
-
-
alpha-phosphoglycerate dehydrogenase
-
-
-
-
D-3-phosphoglycerate dehydrogenase
-
-
-
-
D-3-phosphoglycerate:NAD oxidoreductase
-
-
-
-
dehydrogenase, phosphoglycerate
-
-
-
-
glycerate 3-phosphate dehydrogenase
-
-
-
-
glycerate-1,3-phosphate dehydrogenase
-
-
-
-
PGDH
-
-
-
-
phosphoglycerate oxidoreductase
-
-
-
-
phosphoglyceric acid dehydrogenase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9075-29-0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene serA, ATCC 13032
-
-
Manually annotated by BRENDA team
strain K-12
-
-
Manually annotated by BRENDA team
Frog
-
-
-
Manually annotated by BRENDA team
gene PHGDH
-
-
Manually annotated by BRENDA team
gene PHGDH
UniProt
Manually annotated by BRENDA team
adult male C57BL/6J mice
-
-
Manually annotated by BRENDA team
C57BL/6J mice, gene PHGDH
-
-
Manually annotated by BRENDA team
male ICR mice
-
-
Manually annotated by BRENDA team
Nitrosolobus sp.
gene pgk, several strains, overview
-
-
Manually annotated by BRENDA team
gene pgk, several strains, overview
-
-
Manually annotated by BRENDA team
gene pgk or cbbK, strain ATCC 25196
SwissProt
Manually annotated by BRENDA team
gene pgk, several strains, overview
-
-
Manually annotated by BRENDA team
Nitrosovibrio sp.
gene pgk, several strains, overview
-
-
Manually annotated by BRENDA team
Pigeon
-
-
-
Manually annotated by BRENDA team
Pyrococcus horikoshii DSM 12428
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
O43175
3-PGDH deficiency is a rare recessive inborn error in the biosynthesis of the amino acid L-serine characterized clinically by congenital microcephaly, psychomotor retardation, and intractable seizures. The biochemical abnormalities associated with this disorder are low concentrations of L-serine, D-serine, and glycine in cerebrospinal fluid
malfunction
-
mutations in the human PHGDH cause serine deficiency disorders characterized by severe neurological symptoms including congenital microcephaly and psychomotor retardation, growth retardation phenotypes seen in human patients suffering from SDD caused by PHGDH mutations, overview
malfunction
-
Phgdh null mice have markedly decreased free serine content in their tissues, which is associated with overall growth retardation, striking brain malformation, and embryonic lethality
malfunction
-
targeted disruption of Phgdh in mice causes overall growth retardation with severe brain microcephaly and leads to embryonic lethality
metabolism
-
3-phosphoglycerate dehydrogenase catalyzes the first step of the phosphorylated pathway in the de novo synthesis of L-serine. Availability of L-serine within neural stem/progenitor cells may be a critical factor for neurogenesis in developing and adult brain
metabolism
-
the enzyme is involved in L-serine biosynthesis
metabolism
-
the enzyme is required for the de novo biosynthesis of L-serine
metabolism
O43175
the enzyme is required for the de novo biosynthesis of L-serine
physiological function
O43175
3-PGDH deficiency is a rare recessive inborn error in the biosynthesis of the amino acid L-serine characterized clinically by congenital microcephaly, psychomotor retardation, and intractable seizures. The biochemical abnormalities associated with this disorder are low concentrations of L-serine, D-serine, and glycine in cerebrospinal fluid
physiological function
-
mutations in the human PHGDH cause serine deficiency disorders characterized by severe neurological symptoms including congenital microcephaly and psychomotor retardation
physiological function
-
Phgdh knockout mouse embryos demonstrate that free serine and glycine concentrations are decreased markedly in head samples
physiological function
-
Phgdh null mice have markedly decreased free serine content in their tissues, which is associated with overall growth retardation, striking brain malformation, and embryonic lethality
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-oxoglutarate + NADH
2-hydroxyglutarate + NAD+
show the reaction diagram
-
-
-
-
?
2-oxoglutarate + NADH + H+
2-hydroxyglutarate + NAD+
show the reaction diagram
-
-
-
-
?
2-phospho-D-glycerate + NAD+
2-phosphohydroxypyruvate + NADH + H+
show the reaction diagram
-
activity relative to 3-phospho-D-glycerate: 47%
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
-
-
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
-
r
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first step in biosynthesis of L-serine, pathway regulation, overview
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
P0A9T0
first step in biosynthesis of L-serine, the enzyme contains an ACT domain, which is involved in the allosteric regulation mechanism, residue W139 is involved
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first step in biosynthesis of L-serine, the enzyme contains an ACT domain, which is involved in the allosteric regulation mechanism, residue W139 is involved
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first step in biosynthesis of L-serine, Vmax regulation through domain and subunit changes, overview
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
P0A9T0
D-isomer-specific
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
D-isomer-specific
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH + H+
show the reaction diagram
-
-
-
-
r
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH + H+
show the reaction diagram
-
highest activity
-
-
r
3-phospho-D-glycerate + NADP+
3-phosphohydroxypyruvate + NADPH + H+
show the reaction diagram
-
-
-
-
-
3-phospho-D-glycerate + NADP+
3-phosphohydroxypyruvate + NADPH + H+
show the reaction diagram
-
-
-
-
r
3-phospho-D-glycerate + NADP+
3-phosphohydroxypyruvate + NADPH + H+
show the reaction diagram
Q76KF5
-
-
-
-
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
-
?
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
Q76KF5
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
reduction of hydroxypyruvate-phosphate is faster than oxidation of phosphoglycerate
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
allosteric inhibition by L-serine, L-serine regulates the pathway of serine biosynthesis by end product inhibition interacting with His344, Asn346 and Asn364, 1 serine binds per subunit
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
allosteric inhibition by L-serine, L-serine regulates the pathway of serine biosynthesis by end product inhibition interacting with His344, Asn346 and Asn364, 1 serine binds per subunit
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
-
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
the enzyme catalyzes the first reaction of serine and glycine biosynthesis. SER3 and SER33 encode phosphoglycerate dehydrogenases. The requirement for the SER-dependent phosphoglycerate pathway is conditional since the glyoxylate route of serine/glycine biosynthesis is glucose repressed. Ser33p is likely to be the main isoenzyme of the phosphoglycerate pathway during growth on glucose
-
-
?
3-phosphohydroxypyruvate + NAD+
?
show the reaction diagram
P9WNX3
-
-
-
r
3-phosphohydroxypyruvate + NADH
3-phosphoglycerate + NAD+
show the reaction diagram
-
specific for
-
-
?
alpha-ketoglutarate + NADH
2-hydroxyglutaric acid + NAD+
show the reaction diagram
-
-
-
-
?
alpha-ketoglutarate + NADH
2-hydroxyglutaric acid + NAD+
show the reaction diagram
-
-
-
r
alpha-ketoglutarate + NADH
2-hydroxyglutaric acid + NAD+
show the reaction diagram
-
-
both D- and L-isomer serve as substrate for the reverse reaction, but L-isomer is a poor substrate and probably due to contamination
r
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
-
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
O43175
-
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
-
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
catalytic His280, active site, regulatory, and substrate binding site structures, overview
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
very slow NADH binding in absence of substrate, productive NADH binding, that would support catalytic turnover, is dependent on the presence of substrate, active site structure with the catalytic His280, modelling of ligand-free and substrate-bound active site, overview
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
catalytic His280, active site, regulatory, and substrate binding site structures, overview
-
-
?
DL-glyceraldehyde 3-phosphate + NAD+
?
show the reaction diagram
-
activity relative to 3-phospho-D-glycerate: 9%
-
-
?
additional information
?
-
-
enzyme is involved in de novo L-serine biosynthesis, in the peripheral nervous system and non-neuronal tissues of mice
-
-
-
additional information
?
-
Q76KF5
no activity with 2-oxoglutarate
-
-
-
additional information
?
-
-
no activity with alpha-ketoglutarate
-
-
-
additional information
?
-
-
HOXA10 is required for enzyme regulation in the endometrium
-
-
-
additional information
?
-
O43175
HOXA10 is required for enzyme regulation in the endometrium
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first step in biosynthesis of L-serine, pathway regulation, overview
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
P0A9T0
first step in biosynthesis of L-serine, the enzyme contains an ACT domain, which is involved in the allosteric regulation mechanism, residue W139 is involved
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first step in biosynthesis of L-serine, the enzyme contains an ACT domain, which is involved in the allosteric regulation mechanism, residue W139 is involved
-
-
?
3-phospho-D-glycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first step in biosynthesis of L-serine, Vmax regulation through domain and subunit changes, overview
-
-
?
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
allosteric inhibition by L-serine, L-serine regulates the pathway of serine biosynthesis by end product inhibition interacting with His344, Asn346 and Asn364, 1 serine binds per subunit
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
allosteric inhibition by L-serine, L-serine regulates the pathway of serine biosynthesis by end product inhibition interacting with His344, Asn346 and Asn364, 1 serine binds per subunit
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
-
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
first enzyme in metabolic sequence of synthesis of serine from 3-phosphoglycerate
-
-
r
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
-
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
O43175
-
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
-
-
-
?
phosphonooxypyruvate + NADH + H+
?
show the reaction diagram
-
-
-
-
?
3-phosphoglycerate + NAD+
3-phosphohydroxypyruvate + NADH
show the reaction diagram
-
the enzyme catalyzes the first reaction of serine and glycine biosynthesis. SER3 and SER33 encode phosphoglycerate dehydrogenases. The requirement for the SER-dependent phosphoglycerate pathway is conditional since the glyoxylate route of serine/glycine biosynthesis is glucose repressed. Ser33p is likely to be the main isoenzyme of the phosphoglycerate pathway during growth on glucose
-
-
?
additional information
?
-
-
enzyme is involved in de novo L-serine biosynthesis, in the peripheral nervous system and non-neuronal tissues of mice
-
-
-
additional information
?
-
-
HOXA10 is required for enzyme regulation in the endometrium
-
-
-
additional information
?
-
O43175
HOXA10 is required for enzyme regulation in the endometrium
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-acetylpyridine-NAD+
-
125%
3-acetylpyridine-NAD+
-
199% of the activity with NAD+
3-acetylpyridine-NAD+
-
-
3-acetylpyridine-NADH
-
40% as effective as NADH
3-acetylpyridine-NADH
-
-
deamino-NAD+
-
220%
deamino-NAD+
-
81% of the activity with NAD+
deamino-NAD+
-
-
deamino-NADH
-
as effective as NADH
NAD+
-
-
NAD+
-
-
NAD+
-
hydride ion is transferred to A-site
NAD+
-
cofactor binding structure
NADH
-
-
NADH
-
A-stereospecific for NADH
NADH
-
A-stereospecific for NADH
NADH
-
-
NADH
-
binding of 4 NADH per tetrameric enzyme, negative cooperativity in NADH binding
NADH
-
cofactor binding site structure and binding mechanism, overview
NADH
-
nucleotide binding site structure, overview
NADH
O43175
-
NADH
-
-
NADP+
-
ineffective
NADP+
-
ineffective
NADP+
-
ineffective
NADP+
-
ineffective
NADP+
-
NADP utilization is not observed in the forward reaction even in the presence of high concentrations of 10 mM NADP and 10 mM 3-phospho-D-glycerate
NADPH
-
25% of activity with NADH, can not replace NADH in standard assay concentration
NADPH
-
8% as effective as NADH
NADPH
-
-
NADPH
Q76KF5
less efficiently than NADH
thio-NAD+
-
17.5%
thio-NAD+
-
66% of the activity with NAD+
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cl-
-
stimulates
Cl-
-
stimulates
KCl
Q76KF5
optimal salt concentration is 350-400 mM
MgCl2
-
no effect on enzyme activity, but hinders enzyme inhibition by ATP and ADP
MgCl2
-
stimulates
NaCl
Q76KF5
optimal salt concentration is 350-400 mM
potassium phosphate
-
optimal activity at 75-100 mM, only about 30% of the optimal activity in 5 mM potassium phosphate
SO42-
-
stimulates
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(NH4)2SO4
-
inhibitory effect on NADPH-dependent 3-phosphohydroxypyruvate reduction
(R)-2-amino-1-propanol
-
slightly
3-phosphoglycerate
-
noncompetitive to phosphohydroxypyruvate
3-phosphoglycerate
-
-
3-phosphohydroxypyruvate
Q76KF5
substrate inhibition
3-phosphohydroxypyruvate
-
product inhibition of 3-phospho-D-glycerate oxidation, variable substrate: 3-phospho-D-glycerate, inhibition pattern: competitive; product inhibition of 3-phospho-D-glycerate oxidation, variable substrate: NAD, inhibition pattern: non-competitive
3-phosphohydroxypyruvate
-
uncompetitive substrate inhibition at high substrate concentration
ADP
-
free ADP is more effective than the magnesium complex
ADP
-
weak inhibitory effect on 3-phospho-D-glycerate oxidation, remaining activity: 86%
Ag+
-
inhibition can be overcome by addition of dithiothreitol
AMP
-
weak inhibitory effect on 3-phospho-D-glycerate oxidation, remaining activity: 75%
ATP
-
free ATP is more effective than the magnesium complex
ATP
-
weak inhibitory effect on 3-phospho-D-glycerate oxidation, remaining activity: 85%
beta-Alanine
-
slightly
glycine
-
slightly
glycine
-
-
glycine
-
mutants show less to no inhibition
hydroxyglutarate
-
product inhibition of the alpha-ketoglutarate reduction
iodoacetate
-
-
K2HPO4
-
inhibitory effect on NADPH-dependent 3-phosphohydroxypyruvate reduction. It appears that the phosphate ion PO43- exerts its inhibitory effect by binding to the free enzyme and NADPH-enzyme complex
L-alanine
-
-
L-alanine
-
native enzyme and mutant H344A
L-allothreonine
-
-
L-homoserine
-
-
L-Ser
-
mutant enzyme SerADELTA197, a C-terminally truncated mutant enzyme, shows inhibition
L-Ser
-
binding of the inhibitor to the apoenzyme displays positive cooperativity in the binding of the first two serine molecules and negative cooperativity in the binding of the last two serine molecules. At least two NADH-induced conformational forms of the enzyme bind the inhibitor in the physiological range. Successive binding of NADH to the enzyme results in an increase in the affinity for the first inhibitor ligand bound and a lessening of both the positive and negative cooperativity of inhibitor binding
L-serine
-
non-linear and competitive
L-serine
-
50% inhibition at 0.005 mM and pH 7.5
L-serine
-
inhibition of enzyme from E. coli, Salmonella typhimurium and Haemophilus influenzae, not of mammalian enzyme, inhibition in both reaction directions
L-serine
-
dithiothreitol inhibits enzyme inhibition by serine
L-serine
-
not
L-serine
-
allosteric inhibition, regulates the pathway of serine biosynthesis by end product inhibition interacting with His344, Asn346 and Asn364
L-serine
-
50% inhibition at 0.008 mM L-serine; allosteric inhibition, regulates the pathway of serine biosynthesis by end product inhibition interacting with His344, Asn346 and Asn364
L-serine
-
sigmoidal binding curve with mutant G294V/G336V, mutants with decreased sensitivity to serine
L-serine
-
I0.5: 0.03 mM. In presence of KCl, the binding and the inhibition of L-serine, are cooperative and in the absence of KCl they are not
L-serine
-
feedback regulation of the wild-type enzyme
L-serine
-
feedback regulation, positive and negative cooperativity in absence of NADH, positive in presence of NADH, overview
L-serine
-
the enzyme contains an ACT regulatory domain which binds L-serine for feedback regulation, binding site lies around residues H344-N364
L-serine
-
two serine molecules bound to the regulatory domain, anion- and serine-binding sites between two adjacent subunits
L-serine
-
physiological inhibitor, exerts its effect on at least two steps in the kinetic mechanism. There is a small but significant effect on the dissociation constant of NADH, increasing the Kd to 5 and 23 microM from 0.6 and 9 microM, respectively, for the two sets of sites in the enzyme. After the second substrate is added, serine reduces the amplitude of the signal without a significant effect on the observed rate constants for binding. The serine concentration that reduces the amplitude by 50% is equal to the K0.5 for serine inhibition. Serine binding eliminates a conformational change subsequent to substrate binding by formation of a dead-end quaternary complex consisting of enzyme, coenzyme, substrate, and effector. The rate data conform to a model in which serine can bind to two forms of the enzyme with different affinities
L-threonine
-
-
N-Butylmaleimide
-
-
N-ethylmaleimide
-
-
N-ethylmaleimide
-
D-3-phosphoglycerate and AMP protect against inhibition
N-Heptylmaleimide
-
-
N-Pentylmaleimide
-
-
N-Phenylmaleimide
-
-
NAD+
-
product inhibition, competitive to NADH
NADH
-
inhibition of phosphoglycerate oxidation
NADH
-
product inhibition of 3-phospho-D-glycerate oxidation, variable substrate: 3-phospho-D-glycerate, inhibition pattern: non-competitive; product inhibition of 3-phospho-D-glycerate oxidation, variable substrate: NAD, inhibition pattern: competitive
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxamine 5'-phosphate
-
-
sulfhydryl reagents
-
-
ZnCl2
-
inhibitory effect on 3-phosphohydroxypyruvate reduction, remaining activity: 29%
Mercurials
-
inhibition can be overcome by addition of dithiothreitol
-
additional information
-
Ser, Tyr, Val, Gly, Trp, O-acetyl-L-Ser, and Cys have no effect on enzyme activity in both directions
-
additional information
-
the enzyme contains an ACT domain, which is involved in the allosteric regulation mechanism
-
additional information
-
unlike the Escherichia coli PGDH no inhibition by L-serine
-
additional information
-
mechanism of substrate inhibition, linked to this pH-dependent depression in activity, overview
-
additional information
O43175
substrate inhibition at concentrations above 0.1 mM
-
additional information
O43175
HOAX expression downregulates the enzyme by 40%
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(NH4)2SO4
-
enhancing effect on NAD-dependent 3-phospho-D-glycerate oxidation and 3-phosphohydroxypyruvate reduction but inhibitory effect on NADPH-dependent 3-phosphohydroxypyruvate reduction
HPO42-
-
-
K2HPO4
-
enhancing effect on NAD-dependent 3-phospho-D-glycerate oxidation and 3-phosphohydroxypyruvate reduction but inhibitory effect on NADPH-dependent 3-phosphohydroxypyruvate reduction
L-methionine
-
maximum activation at 10 mM
NaCl
-
PGDH activity increase about 1.5-2.3fold upon the increase of salinity from 0.5 to 2.5 M NaCl
SO42-
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00025
3-acetylpyridine-NAD+
-
25C
0.0054
3-acetylpyridine-NAD+
-
37C
0.00016
3-acetylpyridine-NADH
-
25C
0.033
3-phospho-D-glycerate
-
value for 3-phospho-D-glycerate oxidation using NAD+ as a cofactor
0.19
3-phospho-D-glycerate
-
pH 7.5, mutant G336V
0.23
3-phospho-D-glycerate
-
pH 7.5, mutant H344A
0.26
3-phospho-D-glycerate
-
pH 7.5, mutant A144V
0.28
3-phospho-D-glycerate
-
pH 7.5, mutant E387A
0.29
3-phospho-D-glycerate
-
pH 7.5, mutant N364A
0.3
3-phospho-D-glycerate
-
pH 7.5, mutant E302A
0.33
3-phospho-D-glycerate
-
pH 7.5, mutant R338A
0.35
3-phospho-D-glycerate
-
pH 7.5, mutants A374V and D386A
0.39
3-phospho-D-glycerate
-
pH 7.5, mutant N346A
0.45
3-phospho-D-glycerate
-
pH 7.5, mutant R347A
0.47
3-phospho-D-glycerate
-
pH 7.5, mutant Q361A
0.49
3-phospho-D-glycerate
-
pH 7.5, wild-type enzyme and mutant Q375A
0.58
3-phospho-D-glycerate
-
pH 7.5, mutant P348A
0.63
3-phospho-D-glycerate
-
pH 7.5, mutant S316A
0.64
3-phospho-D-glycerate
-
pH 7.5, mutant G337V
0.66
3-phospho-D-glycerate
-
pH 7.5, mutant E360A
0.68
3-phospho-D-glycerate
-
pH 7.5, mutants S323A and G362V
0.69
3-phospho-D-glycerate
-
pH 7.5, mutant G349V
0.72
3-phospho-D-glycerate
-
pH 7.5, mutant S373A
0.76
3-phospho-D-glycerate
-
pH 7.5, mutant E345A
0.79
3-phospho-D-glycerate
-
pH 7.5, mutant H335A
0.9
3-phospho-D-glycerate
-
-
0.97
3-phospho-D-glycerate
-
pH 7.5, mutant S107A
1.19
3-phospho-D-glycerate
-
pH 7.5, mutant A143V
1.37
3-phospho-D-glycerate
-
pH 7.5, mutant S296A
1.41
3-phospho-D-glycerate
-
pH 7.5, mutants Q298A and N303A
1.6
3-phospho-D-glycerate
-
pH 7.5, mutant D317A
1.77
3-phospho-D-glycerate
-
pH 7.5, mutant E307A
1.99
3-phospho-D-glycerate
-
pH 7.5, mutant E299A
4.33
3-phospho-D-glycerate
-
pH 7.5, mutant S111A
4.78
3-phospho-D-glycerate
-
pH 7.5, mutant Q301A
6.6
3-phospho-D-glycerate
-
pH 7.5, mutant S107A/S111A
7.2
3-phospho-D-glycerate
-
pH 7.5, mutant G145V
12
3-phospho-D-glycerate
-
pH 7.5, mutant K311A
13.1
3-phospho-D-glycerate
-
pH 7.5, mutant N303A/K311A
16.9
3-phospho-D-glycerate
-
pH 7.5, mutant T297A
29.1
3-phospho-D-glycerate
-
pH 7.5, mutant K141A
320
3-phospho-D-glycerate
-
pH 7.5, mutant S111A/K311A
0.212
3-phosphoglycerate
Q76KF5
pH 9.0
0.00013
3-phosphohydroxypyruvate
-
25C
0.0013
3-phosphohydroxypyruvate
-
Km at pH 7.5 is lower than at pH 8.8
0.0032
3-phosphohydroxypyruvate
-
apparent
0.0096
3-phosphohydroxypyruvate
-
value for 3-phosphohydroxypyruvate reduction using NADH as a cofactor
0.015 - 0.02
3-phosphohydroxypyruvate
O43175
pH 7.1, 25C, wild-type enzyme from fibroblasts
0.0216
3-phosphohydroxypyruvate
O43175
pH 7.1, 25C, recombinant FLAG-tagged wild-type enzyme from HEK-293 cells
0.045
3-phosphohydroxypyruvate
-
25C
0.07
3-phosphohydroxypyruvate
-
37C
0.075
3-phosphohydroxypyruvate
-
mutant K439A
0.085
3-phosphohydroxypyruvate
-
pH 7.5, 37C
0.12
3-phosphohydroxypyruvate
-
value for 3-phosphohydroxypyruvate reduction using NADPH as a cofactor
0.123
3-phosphohydroxypyruvate
-
mutant R446A
0.15
3-phosphohydroxypyruvate
-
-
0.16
3-phosphohydroxypyruvate
-
mutant H447A
0.17
3-phosphohydroxypyruvate
-
-
0.18
3-phosphohydroxypyruvate
-
mutant R501A
0.19
3-phosphohydroxypyruvate
-
mutant R451A
0.243
3-phosphohydroxypyruvate
-
mutant R501A/R451A/K439A
0.35
3-phosphohydroxypyruvate
-
pH 7.1
40.2
3-phosphohydroxypyruvate
-
-
0.038
alpha-ketoglutarate
-
apparent, double mutant H344A/N364A
0.042
alpha-ketoglutarate
-
apparent
0.044
alpha-ketoglutarate
-
apparent, mutant N346A
0.088
alpha-ketoglutarate
-
apparent
0.05
D-3-phosphoglycerate
-
-
0.15
D-3-phosphoglycerate
-
pH 7.5
0.29
D-3-phosphoglycerate
-
pH 9.4
1.1
D-3-phosphoglycerate
-
Km at pH 7.5 is lower than at pH 8.8
1.1
D-3-phosphoglycerate
-
-
1.19
D-3-phosphoglycerate
-
pH 9.0
0.0078
NAD+
-
Km at pH 7.5 is lower than at pH 8.8
0.0078
NAD+
-
-
0.008
NAD+
-
-
0.01
NAD+
-
pH 9.0
0.04
NAD+
-
value for 3-phospho-D-glycerate oxidation
0.0867
NAD+
Q76KF5
pH 9.0
0.125
NAD+
-
-
0.25
NAD+
-
pH 9.4
0.5
NAD+
-
-
0.0005
NADH
-
25C
0.0013
NADH
-
value for 3-phosphohydroxypyruvate reduction using NADH as a cofactor
0.0023
NADH
-
25C
0.005
NADH
-
37C
0.01
NADH
-
-
0.012
NADH
-
pH 7.5
0.0177
NADH
Q76KF5
pH 6.5
0.114
NADH
-
pH 7.5, 25C, recombinant mutant G316V
0.12
NADH
-
pH 7.1
0.12
NADH
-
pH 7.5, 25C, recombinant mutant N481A
0.14
NADH
-
pH 7.5, 25C, recombinant mutant D463A
0.165
NADH
-
pH 7.5, 25C, recombinant mutant G317V
0.17
NADH
-
pH 7.5, 25C, wild-type enzyme
0.203
NADH
-
pH 7.5, 25C, recombinant mutant G318V
0.22
NADH
-
pH 7.5, 25C, recombinant mutant G317V/G318V
0.27
NADH
-
pH 7.5, 25C, recombinant mutant Y461A
0.47
NADH
-
pH 7.5, 25C, recombinant mutant G316V/G318V
0.61
NADH
-
pH 7.5, 25C, recombinant mutant G316V/G317V
0.02
NADPH
-
value for 3-phosphohydroxypyruvate reduction using NADPH as a cofactor
0.141
NADPH
Q76KF5
pH 6.5
0.15
NADPH
-
pH 7.5
0.015
phosphohydroxypyruvate
Q76KF5
pH 6.5
1.35
D-3-phosphoglycerate
-
-
additional information
additional information
-
-
-
additional information
additional information
-
stopped flow and steady-state kinetic analysis
-
additional information
additional information
-
kinetic analysis of wild-type and mutant enzymes
-
additional information
additional information
O43175
kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.2
3-phospho-D-glycerate
-
pH 7.5, mutant K141A
4.2
3-phospho-D-glycerate
-
pH 7.5, mutant S111A/K311A
4.6
3-phospho-D-glycerate
-
pH 7.5, mutant D317A
4.9
3-phospho-D-glycerate
-
pH 7.5, mutants E299A and G337V
5.2
3-phospho-D-glycerate
-
pH 7.5, mutant K311A
5.8
3-phospho-D-glycerate
-
pH 7.5, mutant R338A
6
3-phospho-D-glycerate
-
pH 7.5, mutant G349V
6.4
3-phospho-D-glycerate
-
pH 7.5, mutant G362V
7
3-phospho-D-glycerate
-
pH 7.5, mutant T297A
7.4
3-phospho-D-glycerate
-
pH 7.5, mutant S296A
7.5
3-phospho-D-glycerate
-
pH 7.5, mutant S111A
7.8
3-phospho-D-glycerate
-
pH 7.5, mutant H335A
8.6
3-phospho-D-glycerate
-
pH 7.5, mutant A143V
8.7
3-phospho-D-glycerate
-
pH 7.5, mutant G145V
9
3-phospho-D-glycerate
-
pH 7.5, mutants S107A and Q361A
9.3
3-phospho-D-glycerate
-
pH 7.5, mutant P348A
9.6
3-phospho-D-glycerate
-
pH 7.5, mutant N303A/K311A
9.8
3-phospho-D-glycerate
-
pH 7.5, mutant H344A
9.9
3-phospho-D-glycerate
-
pH 7.5, mutant G336V
10.6
3-phospho-D-glycerate
-
pH 7.5, mutant Q301A
10.8
3-phospho-D-glycerate
-
pH 7.5, mutant E360A
11
3-phospho-D-glycerate
-
pH 7.5, mutant S323A
11.2
3-phospho-D-glycerate
-
pH 7.5, mutant E302A
11.4
3-phospho-D-glycerate
-
pH 7.5, mutant S107A/S111A
11.5
3-phospho-D-glycerate
-
pH 7.5, mutants Q298A and S316A
11.7
3-phospho-D-glycerate
-
pH 7.5, mutant A374V
11.8
3-phospho-D-glycerate
-
pH 7.5, mutant N364A
11.9
3-phospho-D-glycerate
-
pH 7.5, mutant E345A; pH 7.5, mutant S373A
12.1
3-phospho-D-glycerate
-
pH 7.5, mutant R347A
12.3
3-phospho-D-glycerate
-
pH 7.5, mutant E307A
12.4
3-phospho-D-glycerate
-
pH 7.5, mutant N303A
12.8
3-phospho-D-glycerate
-
pH 7.5, mutant E387A
13.1
3-phospho-D-glycerate
-
pH 7.5, mutant D386A
13.5
3-phospho-D-glycerate
-
pH 7.5, wild-type enzyme
13.8
3-phospho-D-glycerate
-
pH 7.5, mutant A144V
14.9
3-phospho-D-glycerate
-
pH 7.5, mutant N346A
18.7
3-phospho-D-glycerate
-
pH 7.5, mutant Q375A
0.463
3-phosphohydroxypyruvate
-
apparent
368
3-phosphohydroxypyruvate
-
mutant K439A
467
3-phosphohydroxypyruvate
-
mutant R446A
1446
3-phosphohydroxypyruvate
-
mutant H447A
1558
3-phosphohydroxypyruvate
-
mutant R501A/R451A/K439A
1881
3-phosphohydroxypyruvate
-
mutant R451A
1989
3-phosphohydroxypyruvate
-
mutant R501A
2461
3-phosphohydroxypyruvate
-
-
0.128
alpha-ketoglutarate
-
-
0.137
alpha-ketoglutarate
-
double mutant H344A/N364A
0.32
alpha-ketoglutarate
-
mutant N346A
603
NADH
-
pH 7.5, 25C, recombinant mutant N481A
605
NADH
-
pH 7.5, 25C, recombinant mutant G317V/G318V
720
NADH
-
pH 7.5, 25C, recombinant mutant D463A
1111
NADH
-
pH 7.5, 25C, recombinant mutant G316V
2111
NADH
-
pH 7.5, 25C, recombinant mutant G317V
2349
NADH
-
pH 7.5, 25C, recombinant mutant G318V
2461
NADH
-
pH 7.5, 25C, wild-type enzyme
2754
NADH
-
pH 7.5, 25C, recombinant mutant Y461A
2805
NADH
-
pH 7.5, 25C, recombinant mutant G316V/G317V
2827
NADH
-
pH 7.5, 25C, recombinant mutant G316V/G318V
0.555
alpha-ketoglutarate
-
apparent
additional information
additional information
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.054
3-phosphohydroxypyruvate
-
mutant K439A
0.289
3-phosphohydroxypyruvate
-
mutant R446A
0.87
3-phosphohydroxypyruvate
-
mutant H447A
0.95
3-phosphohydroxypyruvate
-
; mutant R451A
1.02
3-phosphohydroxypyruvate
-
mutant R501A
7.218
3-phosphohydroxypyruvate
-
mutant R501A/R451A/K439A
2
K2HPO4
-
value of phosphate against 3-phosphohydroxypyruvate
10
K2HPO4
-
value of phosphate against NADPH
0.22
L-serine
-
pH 7.5, 25C, recombinant mutant G316V/G318V
0.38
L-serine
-
pH 7.5, 25C, recombinant mutant G316V/G317V
0.42
L-serine
-
pH 7.5, 25C, recombinant mutant Y461A
0.95
L-serine
-
pH 7.5, 25C, wild-type enzyme
1.09
L-serine
-
pH 7.5, 25C, recombinant mutant D463A
1.11
L-serine
-
pH 7.5, 25C, recombinant mutant G317V
1.62
L-serine
-
pH 7.5, 25C, recombinant mutant G317V/G318V
1.925
L-serine
-
pH 7.5, 25C, recombinant mutant G318V
2.231
L-serine
-
pH 7.5, 25C, recombinant mutant G316V
2.32
L-serine
-
pH 7.5, 25C, recombinant mutant N481A
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.14
-
3-phosphoglycerate oxidation, recombinant protein
8.7
-
3-phosphohydroxypyruvate reduction
9.7
-
alpha-ketoglutarate reduction
10.95
-
3-phosphohydroxypyruvate reduction, recombinant protein
21.3
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
during purification an unexpected decline in enzyme activity is observed if the enzyme is stored in plastic tubes, but not in glass ones
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.2
-
enzyme possess a dual pH optimum. A significant decrease in the Ki for substrate inhibition at pH values corresponding to the valley between these optima is responsible for this phenomenon
5.5
-
NADH oxidation
6 - 6.5
Q76KF5
reaction with 3-phosphohydroxypyruvate + NADH
6.1
-
NADH oxidation
7.1
O43175
assay at
7.5
-
3-phosphohydroxypyruvate reduction
8
-
enzyme possess a dual pH optimum. A significant decrease in the Ki for substrate inhibition at pH values corresponding to the valley between these optima is responsible for this phenomenon
8.5
-
initial rate maximum, but enzyme not stable
8.5
-
3-phosphohydroxypyruvate and alpha-ketoglutarate reduction, enzyme and substrate not stable, product inhibition
9
Q76KF5
reaction with 3-phosphoglycerate and NAD+
9.4
-
NAD+ reduction
9.5
-
oxidation of D-3-phosphoglycerate
9.5
-
oxidation of D-3-phosphoglycerate
9.5
-
oxidation of D-3-phosphoglycerate
10
-
3-phospho-D-glycerate oxidation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 7.8
-
about 50% of activity maximum at pH 5 and 7.8, NADH oxidation
5.2 - 5.7
-
at approximately pH 5.7 the activity starts increasing again and reaches a new optimum at approximately pH 5.2 before decreasing once again
5.5 - 8.5
-
Tris buffer and phosphate buffer
6 - 8.5
-
activity drops sharply above pH 8.5
6.5 - 8
-
enzymatic activity decreases below pH 6.5
7.5 - 9.5
-
activity is relatively constant between pH 7.5-9.5. Above pH 9.5 and below pH 7.5 activity falls off rapidly
7.5
-
3-phosphohydroxypyruvate reduction
8.5 - 10.3
-
about 50% of activity maximum at pH 8.5 and 10.3, NAD+ reduction
9
-
3-phospho-D-glycerate oxidation
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
25
-
assay at
25
-
assay at
25
-
assay at
25
-
assay at
25
-
assay at
25
O43175
assay at
45 - 50
-
reduction, but enzyme is thermally unstable, therefore assay is performed at 37C
50
-
assay at
53
-
optimum temperature for 3-phospho-D-glycerate oxidation
80
-
optimum for 3-phosphohydroxypyruvate reduction
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.9
Q76KF5
calculation from nucleotide sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
sustentacular cell
Manually annotated by BRENDA team
-
enzyme expression in the subventricular neural progenitor cells, but not in differentiated neurons. The subventricular neural progenitor cells also show a decline in Phgdh expression in type B and C cells in the aged brain
Manually annotated by BRENDA team
-
Phgdh is constitutively expressed in the brain
Manually annotated by BRENDA team
O43175
high expression levels in the proliferative phase
Manually annotated by BRENDA team
O43175
skin-derived
Manually annotated by BRENDA team
-
satellite cell of the dorsal root ganglia and intestinal nerve plexuses
Manually annotated by BRENDA team
-
located in the rostral migratory stream, high enzyme expression level
Manually annotated by BRENDA team
-
very high expression of Phgdh. It is shown that Phgdh is distributed highly in the renal papilla and inner layer of the outer zone and moderately in the cortex, whereas it is almost negative in the outer layer of the outer zone. This heterogeneous distribution is due to selective expression in distinct tubular segments, i.e., the Bowman's capsule, proximal tubule, and thin limbs of the Henle's loop
Manually annotated by BRENDA team
-
light-grown more than dark-grown
Manually annotated by BRENDA team
-
epithelium
Manually annotated by BRENDA team
-
satellite cell of the dorsal root ganglia and intestinal nerve plexuses
Manually annotated by BRENDA team
-
light-grown more than dark-grown
Manually annotated by BRENDA team
-
of the dorsal root ganglia and intestinal nerve plexuses
Manually annotated by BRENDA team
additional information
-
overview about distribution in animal tissues
Manually annotated by BRENDA team
additional information
-
tissue expression analysis, no expression in absent in committed neuronal precursors, type A cells, derived from type C cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
Brucella abortus (strain 2308)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Lactobacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Ralstonia solanacearum (strain GMI1000)
Sulfolobus tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Vibrio cholerae serotype O1 (strain ATCC 39541 / Classical Ogawa 395 / O395)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35000
-
SDS-PAGE
684698
35000
-
monomer, gel filtration, pH 5
725917
56410
-
deduced from cDNA
687641
57000
-
SDS-PAGE
687641
70000 - 74000
Q76KF5
gel filtration
655484
70000
-
homodimer, gel filtration, pH 7
725917
163000
-
sedimentation equilibrium analysis
287530
165000
-
gel filtration
287525
165000
-
sedimentation equilibrium analysis
287544
166000
-
gel filtration
287537
247000
-
HPLC gel filtration
287539
250000
-
gel filtration
287540
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 57000, SDS-PAGE
?
-
x * 55000, SDS-PAGE
?
-
x * 66453 and 90000, DNA sequence analysis and SDS-PAGE
dimer
Q972A9
-
dimer
O58256
-
dimer
Q76KF5
2 * 33500, calculation from nucleotide sequence
dimer
-
mutant enzyme SerADELTA197
dimer
Pyrococcus horikoshii DSM 12428
-
-
-
homodimer
-
gel filtration
homodimer
-
2 * 35000 at pH 7.0
homotetramer
O43175
4 * 56800
tetramer
-
gel filtration
tetramer
-
4 * 60000, SDS-PAGE
tetramer
-
4 * 40000-50000, sedimentation equilibrium in guanidine-HCl
tetramer
-
4 * 44000, SDS-PAGE, each subunit is divided into 3 separate domains
tetramer
-
4 * 40000-43000, SDS-PAGE, sedimentation equilibrium studies in guanidine hydrochloride
tetramer
-
although the tetramer is composed of identical subunits, significant asymmetry is seen in the tertiary structure of the subunits
tetramer
-
wild-type enzyme
tetramer
-
intervening domains are the two four-stranded beta-sheet structures located next to the substrate binding domains and below the regulatory domains, structure model, overview
tetramer
-
ligand-bound enzyme, sequence comparison
tetramer
-
intervening domains are the two four-stranded beta-sheet structures located next to the substrate binding domains and below the regulatory domains, structure model, overview
-
monomer
-
1 * 35000 at pH 5.0
additional information
-
subunit structure with substrate binding domain, coenzyme binding domain and regulatory domain, active sites
additional information
-
quarternary structure of the active enzyme, conformational changes through domain-domain reorientation, stereochemical model, overview
additional information
-
the enzyme contains an ACT domain, which is involved in the allosteric regulation mechanism
additional information
-
the enzyme contains an ACT regulatory domain, enzyme domain structure
additional information
O43175
each subunit consists of three distinct domains: a cofactor or nucleotide binding domain, a substrate binding domain, and a regulatory domain. Structural molecular modeling of mutant enzymes, overview
additional information
-
the apo-enzyme shows an extreme asymmetry in the orientation of the domains from one subunit to another. The poly glycine stretch in the loop that contains the locus for the 160 rotation leads to subunit asymmetry, structure modelling, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant selenomethionine-labeled enzyme, in presence of 2 mM NAD+ and 5 mM 2-ketoglutarate, euqilibration against precipitation solution containing 1.18-1.25 M ammonium sulfate and 100 mM potassium phosphate, pH 6.4, 18C, 1-2 weeks, X-ray diffraction structure determination and analysis at 2.24 A resolution
-
D-3-phosphoglycerate dehydrogenase with bound effector L-serine or with bound substrate hydroxypyruvic acid phosphate, PGDH at 10 mg/ml is mixed with 5 mM hydroxypyruvic acid phosphate and 5 mM NAD+ analogue 3-acetyl pyridine adenine dinucleotide, or with 5 mM NADH and 5 mM L-serine, from 1 M Na K tartrate, 0.1 M MES, pH 6.5, cryoprotection in 25% propylene glycol, X-ray diffraction structure determination and analysis at resolutions of 2.7 A and 2.4 A, respectively
-
vapor diffusion in hanging drops, structure refined to 2.3 A resolution using SeMet multiwavelength anamolous dispersion
-
crystal structures is determined using X-ray diffraction to resolution of 1.95 A, crystals are grown at room temperature by sitting-drop method
O58256
crystal structure is determined using X-ray diffraction to resolution of 1.77 A, crystals are grown at room temperature by sitting-drop method
Q972A9
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.5 - 11.5
-
enzyme is stable over a wide range of pHs. No decrease in activity after 20 min incubation at 50C
684698
5.5 - 7.5
-
stable
287525
8.5 - 9.5
-
unstable
287525
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
3 min, 40% loss of reductase activity
287546
50 - 80
-
enzyme is highly thermostable, retaining more than 90% of its activity after incubation for 1 h at 80C
684698
additional information
-
activity remains stable after incubation at 40C for 7 min, but decreases to 50% when the enzyme is incubated at 50C for 7 min
687641
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dithiothreitol increases stability
-
dilution inactivates
-
dithiothreitol increases stability
-
inorganic ions, i.e. Cl-, SO42-, HPO42-, essential for stability
-
at low ionic strength the enzyme irreversibly loses activity with time. In 20 mM phosphate buffer, pH 7.5, most of the activity is lost within 24 h. The activity loss is prevented if the ionic strength is kept above approximately 100 mM salt
-
enzyme is highly thermostable
-
dilution inactivates
-
dithiothreitol increases stability
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
purified protein is extremly susceptible to oxidation at alkaline pH
-
287544
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, 50% glycerol, purified recombinant enzyme remains active after 1 month of storage
Q76KF5
-75C, 15% glycerol, purified stable for months
-
4C, purified stable for weeks
-
-80C, 20 mM sodium phosphate buffer, pH 7.2
-
2C, 40% loss of activity, 7 days
-
5C, 60% loss of activity, 24 h
-
-15C, stable for several weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
using ammonium sulphate fractionation and ion exchange chromatography
-
diverse mutants expressed in Escherichia coli
-
PGDH is expressed in Escherichia coli and purified using 5'-AMP-Sepharose affinity chromatography
-
recombinant selenomethionine-labeled enzyme from strain B834
-
partial
-
recombinant tagged wild-type and mutant enzymes
-
using a butyl Sepharose 4 Fast Flow column and a Superdex 200 gel filtration column. During purification an unexpected decline in enzyme activity is observed if the enzyme is stored in plastic tubes, but not in glass ones
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli and Arabidopsis thaliana
-
overexpression in Escherichia coli strain AD494 (DE3), cloning of GFP-mutant with transit peptide, expression in plant
-
gene serA, overexpression in Escherichia coli strains DH5alphaMCR and GM2929, co-overexpression of serA with other enzymes of the L-serine biosynthesis pathway leads to increased L-serine production in Corynebacterium glutamicum mutant serADELAT197
-
expressed in Escherichia coli
-
expression in Escherichia coli
Q76KF5
diverse mutants expressed in Escherichia coli
-
expression as selenomethionine-labeled enzyme in strain B834
-
overexpression of serA gene, that codes for the enzyme, in Escherichia coli strain JM105
-
DNA and amino sequence analysis, phylogenetic analysis, sequence comparisons
-
gene PHGDH consists of 12 exons and maps to chromosome 1p12, enzyme expression analysis in fibroblasts, transient overexpression of FLAG-tagged wild-type and mutant enzymes in HEK-293 cells
O43175
gene PHGDH, quantitative expression analysis in wild-type and mutant mice, genotyping, overview
-
expression in Escherichia coli BL21
-
expression of tagged wild-type and mutant enzymes
-
DNA and amino sequence analysis, phylogenetic analysis, sequence comparisons, expression in Escherichia coli strain JM109
Nitrosolobus sp., Nitrosomonas sp.
-
DNA and amino sequence analysis, phylogenetic analysis, sequence comparisons, expression in Escherichia coli strain JM109
Q4JDI4
DNA and amino sequence analysis, phylogenetic analysis, sequence comparisons, expression in Escherichia coli strain JM109
Nitrosospira sp., Nitrosovibrio sp.
-
expression in Escherichia coli
O58256
expressed in Escherichia coli
-
expression in Escheriochia coli BL21
Q972A9
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
HOXA10 is required for enzyme regulation in the endometrium, HOAX sense expression causes a 2.0fold downregulation of 3-PGDH in endometrial cells
O43175
HOXA10 is required for enzyme regulation in the endometrium, HOAX antisense expression, siRNA, causes a 4.4fold upregulation of 3-PGDH in endometrial cells
O43175
Phgdh knockout mouse embryos demonstrate that free serine and glycine concentrations are decreased markedly in head samples
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E108A
-
in contrast to wild-type mutant existed as monomer even at pH 7
A143A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
A144V
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
A374V
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
D317A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
D386A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
E299A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
E302A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
E307A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
E345A
-
site-directed mutagenesis, mutation of a residue in the serine binding site, the mutant shows only slightly altered kinetics and activity compared to the wild-type enzyme
E360A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
E387A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
G145V
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
G336V
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
G336V
-
changing glycine residues 336 and/or 337 to valine affect the sensitivity of the enzyme to inhibition by L-serine but not the extent of inhibition. The decrease in sensitivity is caused primarily by a decrease in the affinity of the enzyme for L-serine. The mutations also affect the domain rotation of the subunits in response to L-serine binding. Crystal structure of G336V demonstrates that the minimal effect of L-serine binding leading to inhibition of enzyme activity requires a domain rotation of approximately only 6 in just two of the four subunits of the enzyme that are oriented diagonally across from each other in the tetramer
G336V/G337V
-
changing glycine residues 336 and 337 to valine affect the sensitivity of the enzyme to inhibition by L-serine but not the extent of inhibition. The decrease in sensitivity is caused primarily by a decrease in the affinity of the enzyme for L-serine. The mutations also affect the domain rotation of the subunits in response to L-serine binding
G337V
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
G349V
-
site-directed mutagenesis, mutation of a residue in the serine binding site, the mutant shows only slightly altered kinetics and activity compared to the wild-type enzyme
G362V
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
H335A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
H344A
-
50% inhibition at 0.8 mM L-serine
H344A
-
site-directed mutagenesis, mutation of a residue in the serine binding site, the mutant shows only slightly altered kinetics and activity compared to the wild-type enzyme
H344A/N364A
-
no inhibition by L-serine
K141A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
N190A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, no protein expression
N303A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
N303A/K311A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
N346A
-
50% inhibition at 6 mM L-serine
N346A
-
site-directed mutagenesis, mutation of a residue in the serine binding site, the mutant shows only slightly altered kinetics and activity compared to the wild-type enzyme
N346A/H344A
-
no inhibition by L-serine
N346A/N364A
-
no inhibition by L-serine
N364A
-
50% inhibition at 48 mM L-serine
N364A
-
site-directed mutagenesis, mutation of a residue in the serine binding site, the mutant shows only slightly altered kinetics and activity compared to the wild-type enzyme
P348A
-
site-directed mutagenesis, mutation of a residue in the serine binding site, the mutant shows only slightly altered kinetics and activity compared to the wild-type enzyme
Q298A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
Q301A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
Q361A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
Q375A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
R338A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
R347A
-
site-directed mutagenesis, mutation of a residue in the serine binding site, the mutant shows only slightly altered kinetics and activity compared to the wild-type enzyme
S107A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
S107A/S111A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
S111A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
S111A/K311A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
S296A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
S316A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
S323A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
S373A
-
site-directed mutagenesis, mutation of a residue in the Trp-139-loop and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
T297A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
W139F/E360W
-
exhibits catalytic activity comparable to that of the native enzyme and is effectively inhibited by L-serine. The only fluorescence signal of the mutant is due to the single tryptophan at position 360. Pre-steady state analysis of binding of inhibitor serine shows that each serine binding interface produces an integrated fluorescent signal
W139F/E360W/G294V
-
placement of a tryptophanyl residue near the serine binding site (W139F/E360W) allows serine binding to be monitored by fluorescence quenching analysis. Pre-steady state analysis demonstrate that serine binds to two forms of the free enzyme, E and E*. Conversion of Gly-336 to valine has its main effect on the Kd of serine binding to one form of the free enzyme (E) while maintaining the cooperativity of binding observed in the native enzyme
W139F/E360W/G336V
-
placement of a tryptophanyl residue near the serine binding site (W139F/E360W) allows serine binding to be monitored by fluorescence quenching analysis. Pre-steady state analysis demonstrate that serine binds to two forms of the free enzyme, E and E*. Conversion of Gly-294 to valine eliminates a rate limiting conformational change that follows serine binding to E. The conformational change between the two forms of free enzyme is maintained, but the Hill coefficient for cooperativity is significantly lowered
A373T
O43175
naturally occuring mutation located in the nucleotide binding and regulatory domains of 3-PGDH, the mutation does not affect steady-state expression, protein stability, and protein degradation rates, the mutant is almost catalytically inactive
R135W
O43175
naturally occuring mutation located in the nucleotide binding and regulatory domains of 3-PGDH, the mutation does not affect steady-state expression, protein stability, and protein degradation rates, the mutant is almost catalytically inactive
V261M
O43175
naturally occuring mutation located in the nucleotide binding and regulatory domains of 3-PGDH, the mutation does not affect steady-state expression, protein stability, and protein degradation rates, the mutant is almost catalytically inactive
V425M
O43175
naturally occuring mutation in the carboxy-terminal regulatory domain, leads to 3-PGDH deficiency, the mutant is almost catalytically inactive
up
-
Phgdh is transiently upregulated in the brain by kainic acid-treatment, causing selective lesions in the hippocampal region, kainic acid is injected into the bregma, overview
D463A
-
site-directed mutagenesis, a very large reduction in the sensitivity of the mutant enzyme to L-serine
G316V
-
site-directed mutagenesis, the mutant shows slightly reduced activity and decreased sensitivity to L-serine compared to the wild-type
G316V/G317V
-
site-directed mutagenesis, the mutant shows reduced activity and decreased sensitivity to L-serine compared to the wild-type
G316V/G317V/G318V
-
site-directed mutagenesis, the mutant is not producable
G316V/G318V
-
site-directed mutagenesis, the mutant shows reduced activity and decreased sensitivity to L-serine compared to the wild-type
G317V
-
site-directed mutagenesis, the mutant shows slightly reduced activity and decreased sensitivity to L-serine compared to the wild-type
G317V/G318V
-
site-directed mutagenesis, the mutant shows reduced activity and decreased sensitivity to L-serine compared to the wild-type
G318V
-
site-directed mutagenesis, the mutant shows slightly reduced activity and decreased sensitivity to L-serine compared to the wild-type
H447A
-
anion binding site mutant: Km (mM) (3-phosphohydroxypyruvate): 0.16, kcat: 1446, Ki (mM) (3-phosphohydroxypyruvate): 0.87, mutant displays complete uncompetitive substrate inhibition, no dual pH optima compared to wild-type
H447A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
K439A
-
anion binding site mutant: Km (mM) (3-phosphohydroxypyruvate): 0.075, kcat: 368, Ki (mM) (3-phosphohydroxypyruvate): 0.054, mutant displays partial uncompetitive substrate inhibition, mutant retains dual pH optima
K439A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
K439A/R451A/R501A
-
site-directed mutagenesis, the mutation eliminates substrate inhibition and pH-dependent depression in activity
N481A
-
site-directed mutagenesis, a very large reduction in the sensitivity of the mutant enzyme to L-serine. Mutant N481A co-elutes with native PGDH in gel filtration, it shows loss of cooperativity, which cannot be explained by a change in the quaternary structure of the enzyme from tetramer to dimer or monomer
R446A
-
anion binding site mutant: Km (mM) (3-phosphohydroxypyruvate): 0.123 kcat: 467, Ki (mM) (3-phosphohydroxypyruvate): 0.289, mutant displays partial uncompetitive substrate inhibition, no dual pH optima compared to wild-type
R446A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
R451A
-
anion binding site mutant: Km (mM) (3-phosphohydroxypyruvate): 0.19, kcat: 1881, Ki (mM) (3-phosphohydroxypyruvate): 0.95, mutant displays complete uncompetitive substrate inhibition, no dual pH optima compared to wild-type
R451A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
R451A/R501A/K439A
-
site-directed mutagenesis, the mutation eliminates substrate inhibition and pH-dependent depression in activity
R501A
-
anion binding site mutant: Km (mM) (3-phosphohydroxypyruvate): 0.18, kcat: 1989, Ki (mM) (3-phosphohydroxypyruvate): 1.02, mutant displays complete uncompetitive substrate inhibition, no dual pH optima compared to wild-type
R501A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
R501A/R451A/K439A
-
anion binding site mutant: Km (mM) (3-phosphohydroxypyruvate): 0.243, kcat: 1558, Ki (mM) (3-phosphohydroxypyruvate): 7.218, mutant displays only little uncompetitive substrate inhibition, no dual pH optima compared to wild-type
W130F
-
site-directed mutagenesis, catalytically inactive mutant
W29F
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
W327F
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
Y461A
-
site-directed mutagenesis, a very large reduction in the sensitivity of the mutant enzyme to L-serine
H447A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
-
K439A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
-
R446A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
-
R451A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
-
R501A
-
site-directed mutagenesis, the mutant shows altered L-serine binding, kinetics for NADH, and activity compared to the wild-type enzyme
-
additional information
-
expression of the Aphanothece PGDH gene in Escherichia coli causes an increase in levels of betaine as well as glycine and serine. Expression of the Aphanothece PGDH gene in Arabidopsis thaliana, in which the betaine synthetic pathway is introduced via glycine methylation, further increases betaine levels and improves the stress tolerance
additional information
-
expression of GFP-mutant enzyme in Arabidopsis to investigate the tissue distribution, complementation of Escherichia coli serA- mutant
additional information
-
C-terminally truncated SerA-mutant 197 shows phosphoglycerate dehydrogenase activity of 1.3 U/mg protein, the activity is no longer sensitive to L-Ser. The mutant enzyme exists as a dimer
additional information
-
construction of an L-serine-insensitive mutant serADELAT197
K311A
-
site-directed mutagenesis, mutation of a residue in the polypeptide connecting the substrate binding domain and the regulatory domain, the mutant shows altered kinetics and reduced activity compared to the wild-type enzyme
additional information
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diverse mutants with different interaction between the 3 binding domains of each of 4 subunits and modified kinetics
additional information
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diverse mutants with modified active siteand increased Km values
G377S
O43175
naturally occuring mutation located in the nucleotide binding and regulatory domains of 3-PGDH, the mutation does not affect steady-state expression, protein stability, and protein degradation rates, the mutant is almost catalytically inactive
additional information
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sequence analysis of the PHGDH promoter region exhibits several putative transcription factor binding sites for NF-Y, Sp1, GATA-1, p53, AP2, and AP1, with no TATA-box motif at an appropriate position. Transfection of a series of deletion constructs of the promoter region into HeLa cells reveals that the core positive promoter activity resides in the -276 to +1, which contains two GC-motifs for binding Sp1 and one CCAAT-motif for NF-Y. Mutational analysis and electrophoretic mobility shift assay indicates that both the proximal GC-motif and CCAAT-motif are crucial for full induction of the promoter activity
additional information
O43175
p.G238fsX is a naturally occuring frameshift mutation, the mutant is almost catalytically inactive with a 4fold increased Km for 3-phosphohydroxypyruvate
V490M
O43175
naturally occuring mutation in the carboxy-terminal regulatory domain, leads to 3-PGDH deficiency, the mutant is almost catalytically inactive
additional information
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generation of Phgdh heterozygous mice, Phgdh+/-, using E14 embryonic stem cells 129P2/OlaHsd background
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
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results demonstrate that PGDH enhances the levels of betaine by providing the precursor serine for both choline oxidation and glycine methylation pathways
biotechnology
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metabolic engineering of Corynebacterium glutamicum for L-serine production by enzyme overexpression
synthesis
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metabolic engineering of Corynebacterium glutamicum for L-serine production by enzyme overexpression
molecular biology
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results demonstrate that the promoter activity of the human PHGDH gene is positively regulated by the action of transcription factors Sp1 and NF-Y