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Information on EC 2.7.2.3 - phosphoglycerate kinase and Organism(s) Homo sapiens and UniProt Accession P07205
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2.7.2.3 phosphoglycerate kinaseSpecify your search results
Word Map
- 2.7.2.3
- glyceraldehyde-3-phosphate
-
x-linked
- aldolase
- enolase
-
x-chromosome
- hexokinase
- erythrocyte
-
phosphofructokinase
- glucose-6-phosphate
- gapdh
- marrow
-
lentiviral
- anemia
- trypanosoma
- hypoxanthine
-
triosephosphate
-
hematopoietic
- mutase
- glyceraldehyde
- brucei
-
hypoxia-inducible
-
hemolytic
-
phosphoribosyltransferase
- cytomegalovirus
- glycosomal
- triose
-
x-chromosome-linked
- tpi
-
x-inactivation
-
methylation-sensitive
- myoglobinuria
-
n-domain
-
genorm
-
calvin
- hif-1alpha
- hpaii
- mgadp
- fructose-1,6-bisphosphate
-
fructose-bisphosphate
- 2,3-diphosphoglycerate
-
myeloproliferative
-
self-inactivating
-
phosphoglucose
- microbody
-
ligation-mediated
-
atp-generating
-
glucosephosphate
- alpha-enolase
- medicine
- phosphoribulokinase
-
allozyme
- analysis
- biofuel production
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
pgk, phosphoglycerate kinase, pgk-1, 3-phosphoglycerate kinase, phosphoglycerate kinase 1, pgk-2, phosphoglycerate kinase-1, phosphoglycerokinase, phosphoglycerate kinase 2, 3-pgk, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PGK2
3-PGK
-
-
-
-
3-phosphoglycerate kinase
3-phosphoglycerate phosphokinase
-
-
-
-
3-phosphoglyceric acid kinase
-
-
-
-
3-phosphoglyceric acid phosphokinase
-
-
-
-
3-phosphoglyceric kinase
-
-
-
-
ATP-3-phospho-D-glycerate-1-phosphotransferase
-
-
-
-
ATP:D-3-phosphoglycerate 1-phosphotransferase
-
-
-
-
glycerate 3-phosphate kinase
-
-
-
-
glycerophosphate kinase
-
-
-
-
hPGK
kinase (phosphorylating), phosphoglycerate
-
-
-
-
PGK
PGK-1
PGK1
phosphoglycerate kinase
phosphoglycerate kinase 1
phosphoglyceric acid kinase
-
-
-
-
phosphoglyceric kinase
-
-
-
-
phosphoglycerokinase
-
-
-
-
3-phosphoglycerate kinase
-
-
-
-
PGK
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + 3-phospho-D-glycerate = ADP + 3-phospho-D-glyceroyl phosphate
small angle X-ray scattering (SAXS) data on complexes of human PGK (HsPGK) in solution. In combination with deformable elastic network (DEN) refinement a fully open conformation of the apoenzyme is defined, and details are revealed of the relative time spent by the enzyme in the open and closed conformations during catalytic turnover. Together with the crystal structures it is demonstrated that the enzyme strongly favors the open conformation
ATP + 3-phospho-D-glycerate = ADP + 3-phospho-D-glyceroyl phosphate
catalytic mechanism and cycle, conformational changes for substrate binding and positioning, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:3-phospho-D-glycerate 1-phosphotransferase
-
CAS REGISTRY NUMBER
COMMENTARY
9001-83-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2',3'-didehydro-2',3'-dideoxythymidine triphosphate + 3-phospho-D-glycerate
2',3'-didehydro-2',3'-dideoxythymidine diphosphate + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
2',3'-dideoxy-GTP + 3-phospho-D-glycerate
2',3'-dideoxy-GDP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
2'-dATP + 3-phospho-D-glycerate
2'-dADP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
2'-deoxycytidine 5'-triphosphate + 3-phospho-D-glycerate
2'-deoxycytidine 5'-diphosphate + 1,3-diphosphoglycerate
-
-
-
-
?
2'-dGTP + 3-phospho-D-glycerate
2'-dGDP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
2'-dTTP + 3-phospho-D-glycerate
2'-dTDP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
3'-deoxy-3'-azidothymidine triphosphate + 3-phospho-D-glycerate
3'-deoxy-3'-azidothymidine diphosphate + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
acyclovir triphosphate + 3-phospho-D-glycerate
acyclovir diphosphate + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
ADP + 1,3-bisphosphoglycerate
ATP + 3-phosphoglycerate
using the stopped-flow method it is shown that substrate binding kinetics that lead to the formation of the catalytic PGK-1,3-bisphosphoglycerate-ADP complexes are mutually antagonistic with D-ADP, but much less so with L-ADP. A situation that is similar to that for the formation of the abortive PGK-3-phosphoglycerate-ADP complexes
-
-
?
CTP + 3-phospho-D-glycerate
CDP + 1,3-diphosphoglycerate
-
no activity
-
-
?
dATP + 3-phospho-D-glycerate
dADP + 1,3-diphosphoglycerate
-
27% of the activity with ATP
-
-
?
L-2'-dATP + 3-phospho-D-glycerate
L-2'-dADP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
L-2'-dCTP + 3-phospho-D-glycerate
L-2'-dCDP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
r
L-2'-dGTP + 3-phospho-D-glycerate
L-2'-dGDP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
L-2'-dTTP + 3-phospho-D-glycerate
L-2'-dTDP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
L-ADP + 1,3-bisphosphoglycerate
?
with L-ADP, the transient burst phase of ATP is more clear-cut than with D-ADP, suggesting that the product release steps are slower with L-ADP than with D-ADP. This is in accordance with the lower kcat measured with L-ADP compared to D-ADP
-
-
?
L-ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
L-MgADP is almost as a good substrate for hPGK as the natural D-MgADP
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
ADP + 3-phospho-D-glyceroyl 1-phosphate
ATP + 3-phospho-D-glycerate
-
molecular dynamics simulations reveal, that both in the absence and in the presence of ligands the enzyme exhibits a hinge bending type motion but the characteristics of this motion vary considerably. In the apo form, the enzyme exhibits a hinge bending motion of a relatively small amplitude with a time period around 20 ns while the time period of the complexed form is much longer than simulation time. In both cases there is a hinge at the C-terminal side of helix 7, but the hinge points which are near the substrate binding site change upon binding. The apo form is more flexible, there are more hinge points that contribute with similar significance to the hinge bending motion, while in the ternary complex there is only one dominant hinge point. This is located in the vicinity of the substrates, in loop K13. The binding of ADP rigidifies its binding site in the C-domain, while binding 1,3-diphosphoglycerate increases the flexibility of the binding range of the N-domain
-
-
?
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
-
-
-
?
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
-
-
r
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
-
-
?
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
-
-
r
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
responsible for production of ATP during glycolysis
-
r
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
catalytic residue R38, which also binds the substrate 3-phosphoglycerate, is essential in inducing domain closure. Similarly, residues K219, N336, and E343 which interact with the nucleotide substrates are involved in the process of domain closure. The other catalytic residue, K215, covers a large distance during catalysis but has no direct role in domain closure
-
-
?
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
molecular modeling study show that the beta-phosphates of D- and L-ADP have different orientations when bound to the active site of human PGK. The difference is unexpected because L-ADP is almost as catalytically competent as D-ADP
-
-
?
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
the enzyme favors the forward reaction
-
-
r
ATP + 3-phospho-D-glycerate
ADP + 1,3-diphosphoglycerate
-
reaction equilibrium favors ATP production
-
r
ATP + 3-phospho-D-glycerate
ADP + 1,3-diphosphoglycerate
-
absolute specificity for 3-phospho-D-glycerate
-
r
ATP + 3-phospho-D-glycerate
ADP + 1,3-diphosphoglycerate
-
absolute specificity for 3-phospho-D-glycerate
-
r
ATP + 3-phospho-D-glycerate
ADP + 1,3-diphosphoglycerate
-
simultaneous binding of both substrates is essential for domain closure
-
-
r
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
GTP + 3-phospho-D-glycerate
GDP + 1,3-diphosphoglycerate
-
36% of the activity with ATP
-
-
?
GTP + 3-phospho-D-glycerate
GDP + 1,3-diphosphoglycerate
-
60% of the activity with ATP
-
-
?
ITP + 3-phospho-D-glycerate
IDP + 1,3-diphosphoglycerate
-
45% of the activity with ATP
-
-
?
ITP + 3-phospho-D-glycerate
IDP + 1,3-diphosphoglycerate
-
64% of the activity with ATP
-
-
?
UTP + 3-phospho-D-glycerate
UDP + 1,3-diphosphoglycerate
-
only traces of activity
-
-
?
additional information
?
-
-
the only analog of 3-phospho-D-glycerate that can replace the substrate is an artificial 3-phospho-D-glycerate in which the phosphate group-O-PO3H2 is replaced by the phosphomethyl group-CH2-PO3H2, i.e. 2-hydroxy-4-phospho-DL-butyric acid
-
-
?
additional information
?
-
-
reactivity in descending order: ATP, ITP, GTP, dGTP, dATP
-
-
?
additional information
?
-
enzyme is identical with the socalled host factor, which activates RNA transcription in Sendai virus, when bound in a complex with host tubulin and a complementary factor
-
-
?
additional information
?
-
-
enzyme is identical with the socalled host factor, which activates RNA transcription in Sendai virus, when bound in a complex with host tubulin and a complementary factor
-
-
?
additional information
?
-
-
enzyme acts as a disulfide reductase, e.g. plasmin reductase, in tumour angiogenesis
-
-
?
additional information
?
-
-
induction of multidrug resistance in cancer cell lines by overexpression of isozyme PGK1
-
-
?
additional information
?
-
-
the enzyme may be involved in the cellular activation of several antiviral nucleoside analogs including dideoxyinosine, acyclovir, L-2'-deoxycytosine and L-2'-deoxythymidine
-
-
?
additional information
?
-
-
phosphoglycerate kinase 1 is induced by hydrogen peroxide in a dose-dependent manner, while its expression is suppressed by a co-treatment with delphinidin (antioxidant). Several antioxidants, including alpha-tocopherol, butylated hydroxytoluene, and Trolox, also inhibit the PGK1 induction caused by hydrogen peroxide
-
-
?
additional information
?
-
-
Mg-ADP or Mg-beta,gamma-imido-adenosine 5'-triphosphate substitute the substrate Mg-ATP in the ternary complexes, they cannot react with 3-phospho-D-glyceroyl phosphate. Domain closure and substrate antagonism are closely related phenomena for PGK. Conformational rearrangements in the hinge generated by binding of both substrates provide the main driving force for domain closure overcoming the slightly unfavourable contact interactions between the domains
-
-
?
additional information
?
-
-
phosphorylates beta-L-dioxolane-cytidine, a novel L-configuration deoxycytidine analogue, under clinical trials for treating cancer
-
-
?
additional information
?
-
-
molecular dynamics simulations are carried out with four different nucleotides (D-/L-ADP and D-/L-CDP) in complex with hPGK and 1,3-bisphospho-D-glycerate (bPG). The binding affinities of CDPs (both enantiomers) for hPGK are found very weak while D- and L-ADP are better substrates. The binding affinity of the bPG substrate is found to be lower in presence of D-ADP than L-ADP which indicates a potential antagonistic effect on one substrate to the other
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
-
-
r
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
-
-
r
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
-
responsible for production of ATP during glycolysis
-
r
ADP + 3-phospho-D-glyceroyl phosphate
ATP + 3-phospho-D-glycerate
the enzyme favors the forward reaction
-
-
r
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
?
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
ATP + 3-phospho-D-glycerate
ADP + 3-phospho-D-glyceroyl phosphate
-
-
-
r
additional information
?
-
enzyme is identical with the socalled host factor, which activates RNA transcription in Sendai virus, when bound in a complex with host tubulin and a complementary factor
-
-
?
additional information
?
-
-
enzyme is identical with the socalled host factor, which activates RNA transcription in Sendai virus, when bound in a complex with host tubulin and a complementary factor
-
-
?
additional information
?
-
-
enzyme acts as a disulfide reductase, e.g. plasmin reductase, in tumour angiogenesis
-
-
?
additional information
?
-
-
induction of multidrug resistance in cancer cell lines by overexpression of isozyme PGK1
-
-
?
additional information
?
-
-
the enzyme may be involved in the cellular activation of several antiviral nucleoside analogs including dideoxyinosine, acyclovir, L-2'-deoxycytosine and L-2'-deoxythymidine
-
-
?
additional information
?
-
-
phosphoglycerate kinase 1 is induced by hydrogen peroxide in a dose-dependent manner, while its expression is suppressed by a co-treatment with delphinidin (antioxidant). Several antioxidants, including alpha-tocopherol, butylated hydroxytoluene, and Trolox, also inhibit the PGK1 induction caused by hydrogen peroxide
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
in the presence of either beta,gamma-imido-adenosine 5'-triphosphate or ADP binding of 3-phospho-D-glycerate is weakened and the contribution of the entropy-factor to its binding is increased relative to the enthalpy factor
-
ADP
-
-
642235, 642251, 642253, 642261, 642274, 642275, 642276, 642277, 642278, 642280, 642283, 642295, 642300, 706637
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Cd2+
Co2+
divalent cation
Mg2+
Mn2+
Ni2+
Zn2+
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2',3'-dideoxy-2',3'-didehydro-beta-L(-)-5-fluorodeoxycytidine 5'-diphosphate
-
-
nucleoside diphosphates
-
inhibition of ADP formation in decreasing order: GDP, ADP, IDP
shRNA
-
knockdown of PGK, followed by a reduced cytotoxicity of beta-L-dioxolane-cytidine approximately 1.4- and 1.8fold under normoxic and hypoxic conditions, respectively
-
Zn2+
-
ZnATP2- is an alternative substrate to MgATP2-, free metal ions strongly inhibit
AMP
-
noncompetitive with respect to 1,3-diphosphoglycerate, ADP and Mg2+, inhibition kinetics
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
hypoxic treatment induces the protein expression of PGK 3fold, induction of HIF-1alpha by addition of 0.5 mM dimethyloxallyl glycine increases PGK expression under normoxic conditions
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
3-phospho-D-glycerate
-
wild-type, pH and temperature not specified in the publication
0.12
3-phospho-D-glycerate
-
mutant D374A, pH and temperature not specified in the publication
0.16
3-phospho-D-glycerate
isoform PGK-2, pH and temperature not specified in the publication
0.186
3-phospho-D-glycerate
at pH 7.4, temperature not specified in the publication
0.22
3-phospho-D-glycerate
isoform PGK-1, pH and temperature not specified in the publication
0.24
3-phospho-D-glycerate
-
mutant D218A/D374A, pH and temperature not specified in the publication
0.27
3-phospho-D-glycerate
-
mutant D218A, pH and temperature not specified in the publication
0.00686
3-phospho-D-glyceroyl phosphate
at pH 7.4, temperature not specified in the publication
0.077
ADP
-
wild-type, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
0.126
ADP
-
mutant K215A, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
0.017
ATP
-
wild-type, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
0.12
ATP
isoform PGK-1, pH and temperature not specified in the publication
0.2
ATP
-
mutant D218A/D374A, pH and temperature not specified in the publication
0.34
ATP
isoform PGK-2, pH and temperature not specified in the publication
1.6
ATP
-
mutant K215A, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
additional information
additional information
-
Km for ATP at different concentrations
-
additional information
additional information
-
pH-dependence of Km values for the substrates in forward and reverse reaction
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
13.5
3-phospho-D-glycerate
-
co-substrate: ATP, mutant D218A/D374A, pH and temperature not specified in the publication
100
3-phospho-D-glycerate
-
co-substrate: ATP, mutant D218A, pH and temperature not specified in the publication
208
3-phospho-D-glycerate
-
co-substrate: ATP, mutant D374A, pH and temperature not specified in the publication
220
3-phospho-D-glycerate
-
co-substrate: ATP, wild-type, pH and temperature not specified in the publication
0.06
ADP
-
mutant K215A, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
0.78
ADP
-
mutant K215A, at 20°C, in methanol-free buffer, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
200
ADP
-
wild-type, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
2633
ADP
-
wild-type, at 20°C, in methanol-free buffer, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
0.05
ATP
-
mutant K215A, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
0.48
ATP
-
mutant K215A, at 20°C, in methanol-free buffer, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
2.48
ATP
-
wild-type, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
833
ATP
-
wild-type, at 20°C, in methanol-free buffer, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.48
ADP
-
mutant K215A, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
2600
ADP
-
wild-type, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
0.03
ATP
-
mutant K215A, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
150
ATP
-
wild-type, at 4°C, in 30% methanol, 20 mM triethanolamine, pH 7.5, 0.1 M potassium acetate, and 1 mM free Mg2+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Homo sapiens
-
the IC50 values are predicted within a factor of 2 over the 240x experimental range in activity
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
pancreatic carcinoma cell line, low amount of enzyme compared to HT-1080 cells
-
of 10 cancer patients whose serum is tested, 3 of 4 with pancreatic cancer have 65-900% higher levels of PGK1 than that found in normal serum
-
breast carcinoma cell line, reduced amount of enzyme compared to HT-1080 cells
-
pancreatic carcinoma cell line, low amount of enzyme compared to HT-1080 cells
-
colon carcinoma cell line, nearly the same amount of enzyme compared to HT-1080 cells
-
colon carcinoma cell line, increased amount of enzyme compared to HT-1080 cells
-
colon carcinoma cell line, increased amount of enzyme compared to HT-1080 cells
-
breast carcinoma cell line, the same amount of enzyme compared to HT-1080 cells
-
breast carcinoma cell line, low amount of enzyme compared to HT-1080 cells
-
strong expression of PGK1 in more than 70% of the tumors, 7.7- to 11.7fold higher expression in the tumor tissues versus the adjacent nontumor samples
-
clonality analysis of pulmonary sclerosis hemangioma samples with androgen receptor and phosphoglycerate kinase gene polymorphisms and an analysis of gene expression demonstrate that polygonal and surface cuboidal cells in pulmonary sclerosing hemangioma likely arise from a common progenitor
-
levels of PGK1 are significantly higher in pancreatic ductal adenocarcinoma patients than in the control group, patients with gastric cancer have significantly elevated serum levels of PGK1 comparable to those observed in pancreatic ductal adenocarcinoma patients. In breast cancer patients levels of PGK1 are increased only slightly, and show no significant difference in colorectal cancer patients
-
pancreatic carcinoma cell line, very high amount of enzyme compared to HT-1080 cells
additional information
PGK2 is mainly expressed in round spermatids and spermatocytes
testis-specific phosphoglycerate kinase 2. PGK1 and PGK2 have distinct cellular localizations in testicular germ cells. PGK2 is significantly decreased in the testes of elderly men
-
-
remarkably low (less than 5% of normal) PGK enzyme activity level in patients with PGK deficiency
18-year-old man with muscle cramps and recurrent exertional myoglobinuria, without hemolytic anemia or brain dysfunction. PGK deficiency of the patient's erythrocytes, markedly decreased PGK activity
-
primary gastric carcinoma, overexpression of PGK1 and its signalling targets may be a expression-pathway in diffuse primary gastric carcinomas promoting peritoneal dissemination and may function as prognostic markers and/or be potential therapeutic targets to prevent the migration of gastric carcinoma cells into the peritoneum
-
pancreatic carcinoma cell line, the same amount of enzyme compared to HT-1080 cells
-
pancreatic carcinoma cell line, reduced amount of enzyme compared to HT-1080 cells
18-year-old man with muscle cramps and recurrent exertional myoglobinuria, without hemolytic anemia or brain dysfunction. PGK deficiency of the patient's muscle, PGK activity in muscle extracts in patients is less than 10% of normal
PGK1 is mainly expressed in spermatogonia and Sertoli cells
PGK1 and PGK2 had distinct cellular localizations in testicular germ cells. PGK1 is significantly decreased in the testes of elderly men
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
hypoxia has no effect on the subcellular distribution of the PGK protein
-
patients with peritoneal carcinomatosis show a medium to strong nuclear staining for PGK1
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
physiological function
additional information
physiological function
PGK2 is involved in spermatogenesis and is related to sperm motility
physiological function
the enzyme is involved in spermatogenesis and related to sperm motility
malfunction
mutations in hPGK1 cause human PGK1 deficiency, a rate metabolic conformational disease. Most of these mutations cause protein kinetic destabilization by significant changes in the structure/energetics of the transition state for irreversible denaturation. Protein kinetic destabilization by acidic pH is strongly linked to lower thermodynamic stability, while in disease-causing mutations seems to be linked to lower unfolding cooperativity. The plasticity of the hPGK1 denaturation mechanism responds differently to changes in pH and in disease-causing mutations
malfunction
perturbation of enzyme form PGK1 in cancer cells insignificantly affects the conversion of glucose to lactate in glycolysis. Enzyme knockdown does not significantly affect the glycolysis rate, moderately reduces serine consumption and de novo serine synthesis
physiological function
-
PGK1 helps support the interactions between cancer and its microenvironment. A direct and facilitating relationship between CXCL12 and PGK1 levels in the tumor stroma, overexpression of PGK1 increases expression of CXCL12 compared with controls, whereas reducing PGK1 expression decreases expression of CXCL12 levels by cancer-associated fibroblasts. Coimplantation of PGK1-overexpressing fibroblasts with prostate tumor cells promote tumor cell growth in vivo. PGK1 expression in normal fibroblasts stimulates PCalpha proliferation and invasion. Expression of PGK1 and CXCL12 by normal fibroblasts contributes to expression of cancer-associated fibroblast phenotype. Reduced CXCR4 levels in normal fibroblasts that overexpress PGK1
physiological function
-
PGK1 regulates the expression of CXCR4 and beta-catenin at the mRNA and protein levels. PGK1 and CXCR4 regulate their expression reciprocally. Overexpression of PGK1 dramatically increases the invasiveness of gastric cancer cells. Inhibition of CXCR4 in cells overexpressing PGK1 produces only a moderate reduction of invasiveness suggesting that, PGK1 itself has a critical role in tumor invasiveness. PGK1 may be a crucial enzyme in peritoneal dissemination, enhanced expression of PGK1 and its signaling targets CXCR4 and beta-catenin in gastric cancer cells promote peritoneal carcinomatosis
physiological function
-
phosphoglycerate kinase-1 and histone H4 elicit a significant differential humoral response in cancer sera compared with age- and sex-matched sera from normal patients and patients with chronic pancreatitis and diabetes
physiological function
-
3-phosphogycerate kinase is a two domain enzyme, which transfers a phosphate group between its two substrates, 1,3-bisphosphoglycerate bound to the N-domain and ADP bound to the C-domain
physiological function
human phosphoglycerate kinase 1 is a glycolytic enzyme essential for ATP synthesis, and it is implicated in different pathological conditions such as inherited diseases, oncogenesis and activation of drugs for cancer and viral treatments. Enzyme PGK catalyzes the reversible phosphotransfer from ATP to 3-phosphoglycerate yielding ADP and 1,3-biphosphoglycerate, an essential step for ATP synthesis in the glycolytic pathway
physiological function
-
PGK is the enzyme responsible for the first ATP generating step of glycolysis, The enzyme implicated in oncogenesis and the in vivo activation of L-nucleoside pro-drugs effective against retroviruses. Its mechanism requires considerable hinge bending to bring the substrates into proximity in order for phosphoryl transfer to occur. PGK activity is used as a signalling mechanism in oncogenesis, where it displays activity as a disulphide reductase
physiological function
PGK1 is involved in spermatogenesis and is related to sperm motility
physiological function
phosphoglycerate kinase 1 phosphorylates Beclin1 at Ser30 to enhance phosphatidylinositol 3-kinase VPS34 activity and to induce autophagy which is instrumental for brain tumor development
physiological function
the enzyme is involved in spermatogenesis and related to sperm motility
additional information
-
Brownian forces acting on the protein are the dominant factor in the catalytic cycle, the enzyme has evolved measures to harness this force for efficient catalysis. PGK is composed of two domains with the 3-phospho-D-glycerate or 3-phospho-D-glyceroyl phosphate binding site in the N-domain and the nucleotide binding site in the C-domain. In the absence of substrates, the enzyme is in an open conformation in which the two sites are separated and exposed to the solvent for rapid substrate/product exchange. In order for catalysis to occur, hinge bending leads to a closed conformation that results the formation of the active site and the correct placement of the substrates for nucleophilic attack. Structure of open and closed enzyme conformation, modelling, overview
additional information
-
indispensable for the phosphoryl transfer reaction is a large conformational change from an inactive open to an active closed conformation via a hinge motion that should bring substrates into close proximity, molecular dynamics simulations, network-like representation of significant changes in inter-atomic forces, hydrogen-bond network in hinge bending region of apo and complexed hPGK, overview
additional information
protein conformation, thermodynamic and kinetic stability in hPGK1, overview. pH-Dependent linkage between decreased thermal kinetic stability and thermodynamic stability. hPGK1 remains in a native conformation at pH 5-8, but undergoes a conformational transition to a molten globule-like state at acidic pH. hPGK1 kinetic stability remains essentially constant at pH 6-8, but is significantly reduced when pH is decreased from pH 6 to pH 5. This decrease in kinetic stability is caused by significant changes in the energetic/structural balance of the denaturation transition state, which diverge from those found for disease-causing mutations. Protein kinetic destabilization by acidic pH is strongly linked to lower thermodynamic stability, while in disease-causing mutations seems to be linked to lower unfolding cooperativity. The plasticity of the hPGK1 denaturation mechanism responds differently to changes in pH and in disease-causing mutations
additional information
-
protein conformation, thermodynamic and kinetic stability in hPGK1, overview. pH-Dependent linkage between decreased thermal kinetic stability and thermodynamic stability. hPGK1 remains in a native conformation at pH 5-8, but undergoes a conformational transition to a molten globule-like state at acidic pH. hPGK1 kinetic stability remains essentially constant at pH 6-8, but is significantly reduced when pH is decreased from pH 6 to pH 5. This decrease in kinetic stability is caused by significant changes in the energetic/structural balance of the denaturation transition state, which diverge from those found for disease-causing mutations. Protein kinetic destabilization by acidic pH is strongly linked to lower thermodynamic stability, while in disease-causing mutations seems to be linked to lower unfolding cooperativity. The plasticity of the hPGK1 denaturation mechanism responds differently to changes in pH and in disease-causing mutations
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PGK2_HUMAN
417
0
44796
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50000
50000
-
gel filtration, ultracentrifugation, amino acid analysis, tryptophan content
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallization from ammonium sulfate precipitate within 10 min, recrystallization
-
crystallization via precipitation with ammonium sulfate stepwise from 30-35% to 65% w/v within 24 h
-
crystallization via precipitation with ammonium sulfate stepwise from 60% to 75% w/v at room temperature for 2 h, then 4°C, several days
-
crystals of the 3PG-HsPGK binary complex in an open conformation (HsPGK-3PG-open) are grown, and ADP and the nonhydrolyzable ATP analogue, AMP-PCP, are introduced, by soaking, to investigate the effect of their binding on the open conformation
hPGK crystals are obtained at 20 °C by the sitting drop method. A crystal structure of hPGK in a fully closed conformation in complex with L-ADP, 3-phosphoglycerate, and the transition-state analogue AlF4- is determined
mutant enzymes V216F, G166D, M189I, and R38M, hanging drop vapor diffusion method
vapour diffusion in hanging drop method. Crystal structures of hPGK in its free state, or bound to L-ADP, D-ADP, D-CDP or L-CDP
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A199V
the mutant shows a significant decrease of the catalytic efficiency compared to the wild type enzyme
D218A
-
binding of both Mg-free ADP and ATP stronger in the following order: mutant D218A inferiour to mutant D374A inferiour to mutant D218A/D374A. Mutations of D218 or D374 strengthen the binding of MgADP and MgATP to the open conformation of 3-phosphoglycerate kinase. Km (MgATP) similar to wild-type, Km (L-aspartate) increased compared to wild-type, kcat decreased compared to wild-type. Km (Mg2+) increased 3fold compared to wild-type
D218A/D374A
-
binding of both Mg-free ADP and ATP stronger in the following order: mutant D218A inferiour to mutant D374A inferiour to mutant D218A/D374A. Mutations of D218 or D374 strengthen the binding of MgADP and MgATP to the open conformation of 3-phosphoglycerate kinase. Km (MgATP) increased compared to wild-type, Km (L-aspartate) increased compared to wild-type, kcat decreased compared to wild-type. Km (Mg2+) increased 10fold compared to wild-type
D374A
-
binding of both Mg-free ADP and ATP stronger in the following order: mutant D218A inferiour to mutant D374A inferiour to mutant D218A/D374A. Mutations of D218 or D374 strengthen the binding of MgADP and MgATP to the open conformation of 3-phosphoglycerate kinase. Km (MgATP) and Km (L-aspartate) similar to wild-type, kcat similar to wild-type. Km (Mg2+) increased 8fold compared to wild-type
E192A
-
kcat/Km for ATP is 11.7fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 58.6fold lower than wild-type value
E252A
-
specific activity (micromol/min/mg): 220 (wild-type: 420), Tm: 52.1°C, t1/2 (37°C): 7 months. Wild-type: Tm 52.8°C, t1/2(37°C) 3 years
E343A
kcat for reaction with ATP + 3-phosphoglycerate is 58fold lower than wild-type value, kcat for reaction with ADP + 3-phospho-D-glyceroyl phosphate is 31fold lower than wild-type value
F165A
-
kcat/Km for ATP is 23fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 60.7fold lower than wild-type value
F196A
-
kcat/Km for ATP is 4.2fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 19.3fold lower than wild-type value
F241S
the mutant shows a significant decrease of the catalytic efficiency compared to the wild type enzyme
G166D
the mutant shows a significant decrease of the catalytic efficiency compared to the wild type enzyme
I47N
-
specific activity (micromol/min/mg): 90 (wild-type: 420), Tm: 44.6°C, t1/2 (37°C): 27 min. Wild-type: Tm 52.8°C, t1/2(37°C) 3 years
K215A
K219A
kcat for reaction with ATP + 3-phosphoglycerate is 925fold lower than wild-type value, kcat for reaction with ADP + 3-phospho-D-glyceroyl phosphate is 502fold lower than wild-type value
L89P
-
specific activity (micromol/min/mg): 260 (wild-type: 420), Tm: 43°C, t1/2 (37°C): 13 min. Wild-type: Tm 52.8°C, t1/2(37°C) 3 years
M189I
the mutant shows a significant decrease of the catalytic efficiency compared to the wild type enzyme
N336A
R206P
-
naturally occuring mutant variant phosphoglycerate kinase-Uppsala, associated with chronic nonspherocytic hemolytic anemia, structure study via comparison to constructed mutant analogue in yeast
R38A
kcat for reaction with ATP + 3-phosphoglycerate is 1851fold lower than wild-type value, kcat for reaction with ADP + 3-phospho-D-glyceroyl phosphate is 439fold lower than wild-type value
R38M
the mutant shows a significant (10 milion-fold) decrease of the catalytic efficiency compared to the wild type enzyme
R65W
the mutant shows a significant decrease of the catalytic efficiency compared to the wild type enzyme
S392A
-
kcat/Km for ATP is 1.03fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 9.4fold lower than wild-type value
S392A/T393A
-
kcat/Km for ATP is 304fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 1717fold lower than wild-type value
S398A
-
kcat/Km for ATP is 1.13fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 5.3fold lower than wild-type value
T375A
kcat for reaction with ATP + 3-phosphoglycerate is 6.7fold lower than wild-type value, kcat for reaction with ADP + 3-phospho-D-glyceroyl phosphate is 3.9fold lower than wild-type value
T378P
T393A
-
kcat/Km for ATP is 113fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 288fold lower than wild-type value
T393del
-
kcat/Km for ATP is 14615fold lower than wild-type enzyme, kcat/3-phosphoglycerate is 27869fold lower than wild-type value
V216F
the mutant shows a significant decrease of the catalytic efficiency compared to the wild type enzyme
additional information
-
deleted T393, substrate binding abilities are hardly changed, but the substrate antagonism, characteristics of the wild-type enzyme, is completely abolished
K215A
kcat for reaction with ATP + 3-phosphoglycerate is 1735fold lower than wild-type value, kcat for reaction with ADP + 3-phospho-D-glyceroyl phosphate is 3376fold lower than wild-type value
K215A
-
kinetics of substrate binding and the associated protein isomerization steps are fast and identical for the wild-type and mutant K215A. Has a low inherent phosphotransferase activity, with the mutant the conserved Arg 65 replaces the missing Lys 215 by helping to position the transferable phospho group during the reaction. In the mutant the closed conformation of the enzyme is stabilized by a salt bridge between Asp 218 and Arg 170 rather than Arg 65 in the wild-type PGK
N336A
kcat for reaction with ATP + 3-phosphoglycerate is 139fold lower than wild-type value, kcat for reaction with ADP + 3-phospho-D-glyceroyl phosphate is 113fold lower than wild-type value
N336A
-
substrate binding abilities are hardly changed, but the substrate antagonism, characteristics of the wild-type enzyme, is restricted
T378P
pathogenic mutation in patient, biochemical defect of glycolysis associated with episodic cramps and myoglobinuria triggered by strenuous exertion, chronically increased serum creatine kinase levels, and a flat venous lactate response to the forearm ischemic exercise test
T378P
-
specific activity (micromol/min/mg): 65 (wild-type: 420), Tm: 49.8°C, t1/2 (37°C): 3.9 days. Wild-type: Tm 52.8°C, t1/2(37°C) 3 years
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 8
hPGK1 remains in a native conformation at pH 5-8, but undergoes a conformational transition to a molten globule-like state at acidic pH. hPGK1 kinetic stability remains essentially constant at pH 6-8, but is significantly reduced when pH is decreased from pH 6 to pH 5
737784
6.5 - 8
6.5 - 8
-
enzyme in crude hemolysate is stable at 4°C for at least 1 week, inactive below pH 6.0
642261
6.5 - 8
-
crystallized enzyme, solved at a low concentration loses 10% activity per 24 h
642261
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
L-MgADP binds to the specific adenosine-binding site and protects the conformation of hPGK molecule against heat denaturation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
crystalline enzyme is rather unstable, dried crystals or dilute aqueous solutions lose all activity within a few weeks
-
dissolved cyrstallized enzyme at low concentration is rapidly inactivated at neutral pH
-
L-MgADP binds to the specific adenosine-binding site and protects the conformation of hPGK molecule against heat denaturation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, crystals as a suspension in 3 M (NH4)2SO4, 1 mM sodium diphosphate, 1 mM EDTA
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
functional overexpression of isozyme PGK1 in paclitaxel-sensitive, human osteogenic sarcoma cell line U-2OS, inducing a multidrug resistant phenotype
-
normal or cancer-associated fibroblasts infected with the PGK1 or CXCL12 expressing vector
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
spermatozoa from elderly men and young asthenozoospermia patients show decreased expression of phosphoglycerate kinase 2
considerable downregulation of PGK1 expression in siPGK1-treated cells compared to control cells
-
CXCR4 regulates the expression of PGK1. Overexpression of PGK1 in patients with development of peritoneal carcinomatosis
-
in culture, hypoxic treatment induces protein expression of PGK by 3fold but has no effect on the protein expression of other beta-L-dioxolane-cytidine metabolism-associated enzymes such as apurinic/apyrimidinic endonuclease-1, deoxycytidine kinase, CMP kinase, and nM23 H1. Expression of PGK increases as the tumor size increases. PGK protein expression has a positive correlation to HIF-1alpha
-
PGK1 expression is upregulated in cancer-associated fibroblasts versus normal fibroblasts derived from the prostate peripheral zone. Overexpression of CXCL12 in normal fibroblasts and cancer-associated fibroblasts enhances secretion of PGK1 compared with controls
-
reduced CXCL12 expression inhibits PGK1 expression by cancer-associated fibroblasts
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
additional information
-
formation of a double-sided H-bond network, which affects substantially the shape of the main molecular hinge at beta-strand L, under the concerted action of both substrates
analysis
-
first quantitative analysis of the inhibition of human phosphoglycerate kinase by aromatic bisphosphonates by 3D-QSAR (CoMFA, CoMSIA) and pharmacophore modeling methods
analysis
-
development of a sensitive sandwich ELISA using an immuno-affinity-purified chicken polyclonal antibody for capturing PGK1 and an immuno-affinity-purified rabbit polyclonal antibody for detecting it. The sandwich ELISA can be used to quantify PGK1 levels in conditioned media of cell cultures for in vitro PGK1 export studies and in human serum for potential use ascreen for cancer
analysis
-
PGK1 might be a potential protein biomarker of intracellular oxidative status
medicine
-
inhibition of the enzyme can provide a method of treatment for cardiovascular and respiratory disorders, construction of possible specific fluoro-phosphonate inhibitors
medicine
-
overexpression or down-regulation of PGK affects the cytotoxicity of beta-L-dioxolane-cytidine, which is under clinical trials for treating cancer, but not that of beta-D-2',2'-difluorodeoxycytidine under normoxic conditions, overexpression of PGK does not further increase the cytotoxicity of beta-L-dioxolane-cytidine under hypoxic conditions
medicine
PGK deficiency (D164V mutation) is a rare X-linked disease that is characterised by mild to severe haemolytic anaemia, rhabdomyolysis, and variable defects in the central nervous system, it is a recurrent mutation
medicine
-
PGK1 is a potential biomarker and/or therapeutic target for pancreatic ductal adenocarcinoma
medicine
two missense mutations in patients of Spanish origin with a severe life-long chronic haemolytic anaemia associated with progressive neurological impairment. One patient with an amino acid change of Ile to Asn at 46th position from the NH2-terminal serine residue, the second patient with a Ser319Asn amino acid substitution. In both cases, the mutations do not modify any of the PGK binding sites for ATP or 3-phospho-D-glycerate, so their consequence is related to a loss of enzyme stability rather than a decrease of enzyme catalytic function
medicine
-
the gene encoding the erythrocyte enzyme PGK1, is X-linked. Mutations of this gene may cause chronic haemolysis with or without mental retardation and they may cause myopathies, often with episodes of myoglobinuria, or a combination of these clinical manifestations
medicine
the X-linked recessive disease phosphoglycerate kinase deficiency is caused by altered expression of the PGK1 enzyme, which causes muscle stiffness, hemolytic anemia, and mental retardation. The PGK1 gene is charaterized in a family of two brothers, two sisters, and their parents. A single mutation in exon 6, which is associated with the pattern of inheritance of PGK1 deficiency, is observed. This silent G213G mutation is localized to the conserved exon-intron boundary. A method for quantification of PGK1 mRNA is developed. A marked reduction in PGK1 mRNA is demonstrated in both brothers with the disease. A smaller decrease in PGK1 expression is observed in one sister with symptoms of PGK deficiency and in her mother. Only the normal PGK1 allele is expressed in the two heterozygous women. Whereas most known PGK1 mutations cause amino acid alterations, this study indicates that inhibition of the transcription mechanism is the cause of PGK deficiency
medicine
-
PGK1 may serve as prognostic marker and/or be a potential therapeutic target to prevent dissemination of gastric carcinoma cells into the peritoneum
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hashimoto, T.; Yoshikawa, H.
Crystalline phosphogylcerate kinase from human erythrocytes
Biochim. Biophys. Acta
65
355-357
1962
Homo sapiens
Scopes, R.K.
3-Phosphoglycerate kinase
The Enzymes, 3rd. Ed. (Boyer, P. D. , ed. )
8
335-351
1973
Saccharomyces cerevisiae, Cyprinus carpio, Oryctolagus cuniculus, Equus caballus, Esox sp., Frog, Homo sapiens, Pisum sativum, Sus scrofa, Testudinidae
-
Kuntz, G.W.K.; Krietsch, W.K.G.
Phosphoglycerate kinase from animal tissue
Methods Enzymol.
90
103-110
1982
Oryctolagus cuniculus, Equus caballus, Homo sapiens, Mus musculus, trout
-
Ali, M.; Brownstone, Y.S.
A study of phosphoglycerate kinase in human erythrocytes. I. Enzyme isolation, purification and assay
Biochim. Biophys. Acta
445
74-88
1976
Homo sapiens
Ali, M.; Brownstone, Y.S.
A study of phosphoglycerate kinase in human erythrocytes. II. Kinetic properties
Biochim. Biophys. Acta
445
89-103
1976
Homo sapiens
Lee, C.S.; O'Sullivan, W.J.
Properties and mechanism of human erythrocyte phosphoglycerate kinase
J. Biol. Chem.
250
1275-1281
1975
Homo sapiens
Yoshida, A.; Watanabe, S.
Human phosphoglycerate kinase. I. Crystallization and characterization of normal enzyme
J. Biol. Chem.
247
440-445
1972
Homo sapiens
Yoshida, A.; Watanabe, S.; Chen, S.H.; Giblett, E.R.; Malcolm, L.A.
Human phosphoglycerate kinase. II. Structure of a variant enzyme
J. Biol. Chem.
247
446-449
1972
Homo sapiens
Okonkwo, P.O.; Askari, A.; Korngold, L.
Human erythrocyte phosphoglycerate kinase: purification, properties, and interaction with its antibody
Biochim. Biophys. Acta
321
503-511
1973
Homo sapiens
McHarg, J.; Littlechild, J.A.
Studies with inhibitors of the glycolytic enzyme phosphoglycerate kinase for potential treatment of cardiovascular and respiratory disorders
J. Pharm. Pharmacol.
48
201-205
1996
Saccharomyces cerevisiae, Homo sapiens
Ogino, T.; Iwama, M.; Kinouchi, J.; Shibagaki, Y.; Tsukamoto, T.; Mizumoto, K.
Involvement of a cellular glycolytic enzyme, phosphoglycerate kinase, in Sendai virus transcription
J. Biol. Chem.
274
35999-36008
1999
Bos taurus, Saccharomyces cerevisiae, Oryctolagus cuniculus, Homo sapiens (P00558), Homo sapiens
Lay, A.J.; Jiang, X.M.; Kisker, O.; Flynn, E.; Underwood, A.; Condron, R.; Hogg, P.J.
Phosphoglycerate kinase acts in tumor angiogenesis as a disulfide reductase
Nature
408
869-873
2000
Homo sapiens
Tougard, P.; Le, T.H.; Minard, P.; Desmadril, M.; Yon, J.M.; Bizebard, T.; Lebras, G.; Dumas, C.
Structural and functional properties of mutant Arg203Pro from yeast phosphoglycerate kinase, as a model of phosphoglycerate kinase-Uppsala
Protein Eng.
9
181-187
1996
Saccharomyces cerevisiae, Homo sapiens
Duan, Z.; Lamendola, D.E.; Yusuf, R.Z.; Penson, R.T.; Preffer, F.I.; Seiden, M.V.
Overexpression of human phosphoglycerate kinase 1 (PGK1) induces a multidrug resistance phenotype
Anticancer Res.
22
1933-1941
2002
Homo sapiens
Krishnan, P.; Fu, Q.; Lam, W.; Liou, J.Y.; Dutschman, G.; Cheng, Y.C.
Phosphorylation of pyrimidine deoxynucleoside analog diphosphates: selective phosphorylation of L-nucleoside analog diphosphates by 3-phosphoglycerate kinase
J. Biol. Chem.
277
5453-5459
2002
Saccharomyces cerevisiae, Homo sapiens
Gallois-Montbrun, S.; Faraj, A.; Seclaman, E.; Sommadossi, J.P.; Deville-Bonne, D.; Veron, M.
Broad specificity of human phosphoglycerate kinase for antiviral nucleoside analogs
Biochem. Pharmacol.
68
1749-1756
2004
Homo sapiens
Noel, N.; Flanagan, J.M.; Flanagan, J.; Ramirez Bajo, M.J.; Kalko, S.G.; Manu, M.d.e.l.M.; Garcia Fuster, J.L.; Perez de la Ossa, P.; Carreras, J.; Beutler, E.; Vives Corrons, J.L.
Two new phosphoglycerate kinase mutations associated with chronic haemolytic anaemia and neurological dysfunction in two patients from Spain
Br. J. Haematol.
132
523-529
2006
Homo sapiens (P00558), Homo sapiens
Flanagan, J.M.; Rhodes, M.; Wilson, M.; Beutler, E.
The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA
Br. J. Haematol.
134
233-237
2006
Homo sapiens (P00558), Homo sapiens
Varga, A.; Flachner, B.; Konarev, P.; Graczer, E.; Szabo, J.; Svergun, D.; Zavodszky, P.; Vas, M.
Substrate-induced double sided H-bond network as a means of domain closure in 3-phosphoglycerate kinase
FEBS Lett.
580
2698-2706
2006
Homo sapiens
Kotsikorou, E.; Sahota, G.; Oldfield, E.
Bisphosphonate inhibition of phosphoglycerate kinase: quantitative structure-activity relationship and pharmacophore modeling investigation
J. Med. Chem.
49
6692-6703
2006
Saccharomyces cerevisiae, Homo sapiens, Trypanosoma brucei (P07378)
Lam, W.; Leung, C.H.; Bussom, S.; Cheng, Y.C.
The impact of hypoxic treatment on the expression of phosphoglycerate kinase and the cytotoxicity of troxacitabine and gemcitabine
Mol. Pharmacol.
72
536-544
2007
Homo sapiens
Hwang, T.L.; Liang, Y.; Chien, K.Y.; Yu, J.S.
Overexpression and elevated serum levels of phosphoglycerate kinase 1 in pancreatic ductal adenocarcinoma
Proteomics
6
2259-2272
2006
Homo sapiens
Varga, A.; Szabo, J.; Flachner, B.; Roy, B.; Konarev, P.; Svergun, D.; Zavodszky, P.; Perigaud, C.; Barman, T.; Lionne, C.; Vas, M.
Interaction of human 3-phosphoglycerate kinase with L-ADP, the mirror image of D-ADP
Biochem. Biophys. Res. Commun.
366
994-1000
2008
Homo sapiens
Gondeau, C.; Chaloin, L.; Varga, A.; Roy, B.; Lallemand, P.; Perigaud, C.; Barman, T.; Vas, M.; Lionne, C.
Differences in the transient kinetics of the binding of D-ADP and its mirror image L-ADP to human 3-phosphoglycerate kinase revealed by the presence of 3-phosphoglycerate
Biochemistry
47
3462-3473
2008
Homo sapiens (P00558), Homo sapiens
Szabo, J.; Varga, A.; Flachner, B.; Konarev, P.V.; Svergun, D.I.; Zavodszky, P.; Vas, M.
Communication between the nucleotide site and the main molecular hinge of 3-phosphoglycerate kinase
Biochemistry
47
6735-6744
2008
Homo sapiens (P00558), Homo sapiens
Jang, C.H.; Lee, I.A.; Ha, Y.R.; Lim, J.; Sung, M.K.; Lee, S.J.; Kim, J.S.
PGK1 induction by a hydrogen peroxide treatment is suppressed by antioxidants in human colon carcinoma cells
Biosci. Biotechnol. Biochem.
72
1799-1808
2008
Homo sapiens
Zieker, D.; Koenigsrainer, I.; Traub, F.; Nieselt, K.; Knapp, B.; Schillinger, C.; Stirnkorb, C.; Fend, F.; Northoff, H.; Kupka, S.; Bruecher, B.L.; Koenigsrainer, A.
PGK1 a potential marker for peritoneal dissemination in gastric cancer
Cell. Physiol. Biochem.
21
429-436
2008
Homo sapiens
Szabo, J.; Varga, A.; Flachner, B.; Konarev, P.V.; Svergun, D.I.; Zavodszky, P.; Vas, M.
Role of side-chains in the operation of the main molecular hinge of 3-phosphoglycerate kinase
FEBS Lett.
582
1335-1340
2008
Homo sapiens
Zhao, W.; Pao, S.; Malik, F.; Soh, J.; Fernandez, S.; Chirico, W.J.
A sandwich ELISA for phosphoglycerate kinase
J. Immunoassay Immunochem.
29
220-233
2008
Homo sapiens
Wang, E.H.; Dai, S.D.; Qi, F.J.; Hong-Tao, X.; Wei, Q.
Gene expression and clonality analysis of the androgen receptor and phosphoglycerate kinase genes in polygonal cells and cuboidal cells in so-called pulmonary sclerosing hemangioma
Mod. Pathol.
20
1208-1215
2007
Homo sapiens
Svaasand, E.K.; Aasly, J.; Landsem, V.M.; Klungland, H.
Altered expression of PGK1 in a family with phosphoglycerate kinase deficiency
Muscle Nerve
36
679-684
2007
Homo sapiens (P00558), Homo sapiens
Gondeau, C.; Chaloin, L.; Lallemand, P.; Roy, B.; Perigaud, C.; Barman, T.; Varga, A.; Vas, M.; Lionne, C.; Arold, S.T.
Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase
Nucleic Acids Res.
36
3620-3629
2008
Homo sapiens (P00558), Homo sapiens
Varga, A.; Lionne, C.; Lallemand, P.; Szabo, J.; Adamek, N.; Valentin, C.; Vas, M.; Barman, T.; Chaloin, L.
Direct kinetic evidence that lysine 215 is involved in the phospho-transfer step of human 3-phosphoglycerate kinase
Biochemistry
48
6998-7008
2009
Homo sapiens
Wang, J.; Ying, G.; Wang, J.; Jung, Y.; Lu, J.; Zhu, J.; Pienta, K.J.; Taichman, R.S.
Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression
Cancer Res.
70
471-480
2010
Homo sapiens
Patwa, T.H.; Li, C.; Poisson, L.M.; Kim, H.Y.; Pal, M.; Ghosh, D.; Simeone, D.M.; Lubman, D.M.
The identification of phosphoglycerate kinase-1 and histone H4 autoantibodies in pancreatic cancer patient serum using a natural protein microarray
Electrophoresis
30
2215-2226
2009
Homo sapiens
Varga, A.; Szabo, J.; Flachner, B.; Gugolya, Z.; Vonderviszt, F.; Zavodszky, P.; Vas, M.
Thermodynamic analysis of substrate induced domain closure of 3-phosphoglycerate kinase
FEBS Lett.
583
3660-3664
2009
Homo sapiens
Zieker, D.; Koenigsrainer, I.; Tritschler, I.; Loeffler, M.; Beckert, S.; Traub, F.; Nieselt, K.; Buehler, S.; Weller, M.; Gaedcke, J.; Taichman, R.S.; Northoff, H.; Bruecher, B.L.; Koenigsrainer, A.
Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer
Int. J. Cancer
126
1513-1520
2010
Homo sapiens
Lam, W.; Bussom, S.; Cheng, Y.C.
Effect of hypoxia on the expression of phosphoglycerate kinase and antitumor activity of troxacitabine and gemcitabine in non-small cell lung carcinoma
Mol. Cancer Ther.
8
415-423
2009
Homo sapiens
Spiegel, R.; Gomez, E.A.; Akman, H.O.; Krishna, S.; Horovitz, Y.; DiMauro, S.
Myopathic form of phosphoglycerate kinase (PGK) deficiency: a new case and pathogenic considerations
Neuromuscul. Disord.
19
207-211
2009
Homo sapiens (P00558), Homo sapiens
Palmai, Z.; Chaloin, L.; Lionne, C.; Fidy, J.; Perahia, D.; Balog, E.
Substrate binding modifies the hinge bending characteristics of human 3-phosphoglycerate kinase: A molecular dynamics study
Proteins Struct. Funct. Bioinform.
77
319-329
2009
Homo sapiens
Palmai, Z.; Perahia, D.; Lionne, C.; Fidy, J.; Balog, E.; Chaloin, L.
Ligand chirality effects on the dynamics of human 3-phosphoglycerate kinase: comparison between D- and L-nucleotides
Arch. Biochem. Biophys.
511
88-100
2011
Homo sapiens
Varga, A.; Palmai, Z.; Gugolya, Z.; Graczer, E.; Vonderviszt, F.; Zavodszky, P.; Balog, E.; Vas, M.
Importance of aspartate residues in balancing the flexibility and fine-tuning the catalysis of human 3-phosphoglycerate kinase
Biochemistry
51
10197-10207
2012
Homo sapiens
Pey, A.L.; Mesa-Torres, N.; Chiarelli, L.R.; Valentini, G.
Structural and energetic basis of protein kinetic destabilization in human phosphoglycerate kinase 1 deficiency
Biochemistry
52
1160-1170
2013
Homo sapiens
Zerrad, L.; Merli, A.; Schroeder, G.F.; Varga, A.; Graczer, E.; Pernot, P.; Round, A.; Vas, M.; Bowler, M.W.
A spring-loaded release mechanism regulates domain movement and catalysis in phosphoglycerate kinase
J. Biol. Chem.
286
14040-14048
2011
Homo sapiens (P00558)
Lallemand, P.; Chaloin, L.; Roy, B.; Barman, T.; Bowler, M.W.; Lionne, C.
Interaction of human 3-phosphoglycerate kinase with its two substrates: is substrate antagonism a kinetic advantage?
J. Mol. Biol.
409
742-757
2011
Homo sapiens (P00558), Homo sapiens
Pey, A.L.
pH-dependent relationship between thermodynamic and kinetic stability in the denaturation of human phosphoglycerate kinase 1
Biochimie
103
7-15
2014
Homo sapiens (P00558), Homo sapiens
Bowler, M.W.
Conformational dynamics in phosphoglycerate kinase, an open and shut case?
FEBS Lett.
587
1878-1883
2013
Homo sapiens
Liu, X.X.; Zhang, H.; Shen, X.F.; Liu, F.J.; Liu, J.; Wang, W.J.
Characteristics of testis-specific phosphoglycerate kinase 2 and its association with human sperm quality
Hum. Reprod.
31
273-279
2016
Homo sapiens (P00558), Homo sapiens (P07205), Homo sapiens
Palmai, Z.; Seifert, C.; Graeter, F.; Balog, E.
An allosteric signaling pathway of human 3-phosphoglycerate kinase from force distribution analysis
PLoS Comput. Biol.
10
e1003444
2014
Homo sapiens
Liu, X.; Zhang, H.; Shen, X.; Liu, F.; Liu, J.; Wang, W.
Characteristics of testis-specific phosphoglycerate kinase 2 and its association with human sperm quality
Hum. Reprod.
31
273-279
2016
Homo sapiens (P00558), Homo sapiens (P07205), Homo sapiens
Jin, C.; Zhu, X.; Wu, H.; Wang, Y.; Hu, X.
Perturbation of phosphoglycerate kinase 1 (PGK1) only marginally affects glycolysis in cancer cells
J. Biol. Chem.
295
6425-6446
2020
Saccharomyces cerevisiae, Homo sapiens (P00558), Homo sapiens
Qian, X.; Li, X.; Cai, Q.; Zhang, C.; Yu, Q.; Jiang, Y.; Lee, J.H.; Hawke, D.; Wang, Y.; Xia, Y.; Zheng, Y.; Jiang, B.H.; Liu, D.X.; Jiang, T.; Lu, Z.
Phosphoglycerate kinase 1 phosphorylates Beclin1 to induce autophagy
Mol. Cell
65
917-931.e6
2017
Homo sapiens (P00558)
Rojas-Pirela, M.; Andrade-Alviarez, D.; Rojas, V.; Kemmerling, U.; Caceres, A.J.; Michels, P.A.; Concepcion, J.L.; Quinones, W.
Phosphoglycerate kinase structural aspects and functions, with special emphasis on the enzyme from Kinetoplastea
Open Biology
10
200302
2020
Geobacillus stearothermophilus, Corynebacterium glutamicum, Oryctolagus cuniculus, Leishmania mexicana mexicana, Phaeodactylum tricornutum, Spinacia oleracea, Spirulina geitleri, Synechocystis sp. PCC 6803, Thermotoga maritima, Zymomonas mobilis, Trypanosoma rangeli (A0A061J5A1), Trypanosoma rangeli (A0A061J9D5), Entamoeba histolytica (N9V9W5), Homo sapiens (P00558), Saccharomyces cerevisiae (P00560), Trypanosoma brucei brucei (P07377), Trypanosoma brucei brucei (P07378), Thermus thermophilus (P09403), Leishmania major (Q27683), Trypanosoma cruzi (Q4D192), Trypanosoma cruzi (Q4D193), Trypanosoma cruzi, Pseudomonas sp. 'TAC II 18' (Q9RBS3), Entamoeba histolytica HM-1:IMSS-A (N9V9W5), Trypanosoma cruzi CL-Brener (Q4D192), Trypanosoma cruzi CL-Brener (Q4D193), Trypanosoma rangeli SC58 (A0A061J5A1), Trypanosoma rangeli SC58 (A0A061J9D5)
Fiorillo, A.; Petrosino, M.; Ilari, A.; Pasquo, A.; Cipollone, A.; Maggi, M.; Chiaraluce, R.; Consalvi, V.
The phosphoglycerate kinase 1 variants found in carcinoma cells display different catalytic activity and conformational stability compared to the native enzyme
PLoS ONE
13
e0199191
2018
Homo sapiens (P00558)
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