Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GMP + NADPH + H+
IMP + NH3 + NADP+
IMP + NH3 + NADP+
GMP + NADPH + H+
-
-
-
r
dGMP + NADPH + H+
dIMP + NH3 + NADP+
dGMP is a poor substrate
-
-
r
dIMP + NH3 + NADP+
dGMP + NADPH + H+
dIMP is a poor substrate
-
-
r
GMP + NADPH + H+
IMP + NH3 + NADP+
IMP + NH3 + NADP+
GMP + NADPH + H+
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
r
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
r
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
r
IMP + NH3 + NADP+
GMP + NADPH + H+
-
-
-
r
IMP + NH3 + NADP+
GMP + NADPH + H+
-
-
-
r
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
ir
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
-
ir
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
ir
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
less than 10% of the NADPH rate: thionicotinamide-NADPH, deamino-NADPH, 3-acetylpyrimidine-NADPH
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
arabinosylGMP, 2'-dGMP and 8-azaGMP are reductively deaminated to their corresponding IMP analog at rates 1-2% the rate with GMP
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
essential for the salvage pathway of purine ribonucleotide biosynthesis
-
-
ir
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
important for the maintenance of the intracellular adenine guanine balance, possible role in the regulation of differentiation of leukemia cells
-
-
ir
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Alzheimer Disease
Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer's disease.
Breast Neoplasms
Lack of expression of the proteins GMPR2 and PPAR? are associated with the basal phenotype and patient outcome in breast cancer.
Carcinogenesis
Lack of expression of the proteins GMPR2 and PPAR? are associated with the basal phenotype and patient outcome in breast cancer.
Carcinoma, Hepatocellular
Methotrexate decreases thymidine kinase activity.
Gout
Erythrocyte adenosine kinase activity in gout.
Leukemia
Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells.
Leukemia
Reciprocal alterations of GMP reductase and IMP dehydrogenase activities during differentiation in HL-60 leukemia cells.
Leukemia, Myeloid, Acute
An integrated map of human chromosome 6p23.
Melanoma
A purine nucleotide biosynthesis enzyme guanosine monophosphate reductase is a suppressor of melanoma invasion.
Neoplasms
Characterizing and optimizing human anticancer drug targets based on topological properties in the context of biological pathways.
Neoplasms
Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells.
Neoplasms
Diverse proteomic alterations in gastric adenocarcinoma.
Spinocerebellar Ataxias
An integrated map of human chromosome 6p23.
Starvation
Inhibition of cellular growth by increased guanine nucleotide pools. Characterization of an Escherichia coli mutant with a guanosine kinase that is insensitive to feedback inhibition by GTP.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.0348
NADPH
pH 8.0, 35°C
0.015
dGMP
wild type enzyme, at pH 7.8 and 25°C
0.14
dIMP
wild type enzyme, at pH 7.8 and 25°C
additional information
additional information
-
0.0026
GMP
-
-
0.0032
GMP
wild type enzyme, at pH 7.8 and 25°C
0.0075
GMP
-
data from the low concentration range
0.38
GMP
mutant enzyme D219A, at pH 7.8 and 25°C
0.023
IMP
wild type enzyme, at pH 7.8 and 25°C
1.1
IMP
mutant enzyme D219A, at pH 7.8 and 25°C
0.05
NADP+
wild type enzyme, with IMP and NH3 as cosubstrates, at pH 7.8 and 25°C
0.109
NADP+
wild type enzyme, with IMP and NH3 as cosubstrates, at pH 7.8 and 25°C
0.42
NADP+
mutant enzyme D219A, with IMP and NH3 as cosubstrates, at pH 7.8 and 25°C
0.0085
NADPH
-
-
0.016
NADPH
wild type enzyme, with GMP as cosubstrate, at pH 7.8 and 25°C
0.0293
NADPH
pH 8.0, 35°C
0.101
NADPH
wild type enzyme, with GMP as cosubstrate, at pH 7.8 and 25°C
0.12
NADPH
mutant enzyme D219A, with GMP as cosubstrate, at pH 7.8 and 25°C
additional information
additional information
Michaelis-Menten steady-state kinetics
-
additional information
additional information
Michaelis-Menten steady-state kinetics
-
additional information
additional information
Michaelis-Menten steady-state kinetics
-
additional information
additional information
Michaelis-Menten steady-state kinetics
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
GMPR shows high similarities in amino acid sequence and structure to inosine 5'-monophosphate dehydrogenase (IMPDH), EC 1.1.1.205, the enzyme catalyzing the NAD+-dependent oxidation of IMP to xanthosine 5'-monophosphate (XMP). But GMPR and IMPDH are generally distinguished by the cystathionine beta-synthase (CBS) domain, which is well conserved in IMPDHs but absent in GMPRs
metabolism
the enzyme activity establishes a link between guanosine metabolism and RHOGTPase-dependent melanoma cell invasion
physiological function
GMPR downregulates the amounts of several GTP-bound (active) RHO-GTPases, and suppresses the ability of melanoma cells to form invadopodia, to degrade extracellular matrix and invade in vitro, and to grow as tumor xenografts in vivo. Enzyme GMPR partially depletes intracellular GTP pools. GMPR is a melanoma invasion suppressor, its enzymatic activity affects melanoma cell invasion and melanoma cell tumorigenicity. GMPR affects formation of invadopodia and matrix degradation. GMPR differentially regulates activity of several RHO-family GTPases, overview
evolution
GMPR shows high similarities in amino acid sequence and structure to inosine 5'-monophosphate dehydrogenase (IMPDH), EC 1.1.1.205, the enzyme catalyzing the NAD+-dependent oxidation of IMP to xanthosine 5'-monophosphate (XMP). But GMPR and IMPDH are generally distinguished by the cystathionine beta-synthase (CBS) domain, which is well conserved in IMPDHs but absent in GMPRs
additional information
kinetics and dynamics of GMP, IMP, and NADP+ when bound to enzyme GMPR: IMP and GMP are in fast exchange with GMPR. Analysis of interactions of substrate and cofactors with GMPR, epitope mapping, overview. Dynamic properties of ternary complexes in hydride transfer and deamination
malfunction
expression of guanosine monophosphate reductase (GMPR), an enzyme involved in de novo biosynthesis of purine nucleotides, is downregulated in invasive stages of human melanoma. Overexpression of catalytically inactive mutant GMPRC186A at levels comparable to overexpression of wild-type GMPR does not affect invasion in of melanoma cells
malfunction
an enzyme mutation causes aberrant splicing, decreased enzyme protein levels in skeletal muscle of patient with autosomal dominant progressive external ophthalmoplegia, proliferating and quiescent cells, and is associated with subtle changes in nucleotide homeostasis protein levels and evidence of disturbed mitochondrial DNA maintenance in skeletal muscle
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Spector, T.; Jones, T.E.; Miller, R.L.
Reaction mechanism and specificity of human GMP reductase. Substrates, inhibitors, activators, and inactivators
J. Biol. Chem.
254
2308-2315
1979
Homo sapiens
brenda
Mackenzie, J.J.; Sorensen, L.B.
Guanosine 5-phosphate reductase of human erythrocytes
Biochim. Biophys. Acta
327
282-294
1973
Homo sapiens
brenda
Deng, Y.; Wang, Z.; Ying, K.; Gu, S.; Ji, C.; Huang, Y.; Gu, X.; Wang, Y.; Xu, Y.; Li, Y.; Xie, Y.; Mao, Y.
NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression, purification, and kinetic properties
Int. J. Biochem. Cell Biol.
34
1035-1050
2002
Homo sapiens, Homo sapiens (Q9P2T1), no activity in Haemophilus influenzae, no activity in Methanocaldococcus jannaschii, no activity in Mycoplasma genitalium
brenda
Ji, C.N.; Ying, G.; Deng, Y.F.; Chen, S.; Zhang, W.H.; Shu, G.; Xie, Y.; Mao, Y.M.
Purification, crystallization and preliminary X-ray studies of GMP reductase 2 from human
Acta Crystallogr. Sect. D
59
1109-1110
2003
Homo sapiens
brenda
Zhang, J.; Zhang, W.; Zou, D.; Chen, G.; Wan, T.; Zhang, M.; Cao, X.
Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells
J. Cancer Res. Clin. Oncol.
129
76-83
2003
Homo sapiens (Q9P2T1), Homo sapiens
brenda
Li, J.; Wei, Z.; Zheng, M.; Gu, X.; Deng, Y.; Qiu, R.; Chen, F.; Ji, C.; Gong, W.; Xie, Y.; Mao, Y.
Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP
J. Mol. Biol.
355
980-988
2006
Homo sapiens
brenda
Wawrzyniak, J.A.; Bianchi-Smiraglia, A.; Bshara, W.; Mannava, S.; Ackroyd, J.; Bagati, A.; Omilian, A.R.; Im, M.; Fedtsova, N.; Miecznikowski, J.C.; Moparthy, K.C.; Zucker, S.N.; Zhu, Q.; Kozlova, N.I.; Berman, A.E.; Hoek, K.S.; Gudkov, A.V.; Shewach, D.S.; Morrison, C.D.; Nikiforov, M.A.
A purine nucleotide biosynthesis enzyme guanosine monophosphate reductase is a suppressor of melanoma invasion
Cell Rep.
5
493-507
2013
Homo sapiens (P36959), Homo sapiens
brenda
Rosenberg, M.M.; Redfield, A.G.; Roberts, M.F.; Hedstrom, L.
Substrate and Cofactor Dynamics on Guanosine Monophosphate Reductase Probed by High Resolution Field Cycling 31P NMR Relaxometry
J. Biol. Chem.
291
22988-22998
2016
Homo sapiens (Q9P2T1)
brenda
Bessho, T.; Okada, T.; Kimura, C.; Shinohara, T.; Tomiyama, A.; Imamura, A.; Kuwamura, M.; Nishimura, K.; Fujimori, K.; Shuto, S.; Ishibashi, O.; Kubata, B.K.; Inui, T.
Novel characteristics of Trypanosoma brucei guanosine 5-monophosphate reductase distinct from host animals
PLoS Negl. Trop. Dis.
10
e0004339
2016
Homo sapiens (P36959), Homo sapiens (Q9P2T1), Trypanosoma brucei brucei (Q57ZS7), Trypanosoma brucei brucei 927/4 GUTat10.1 (Q57ZS7)
brenda
Rosenberg, M.M.; Redfield, A.G.; Roberts, M.F.; Hedstrom, L.
Dynamic characteristics of guanosine-5'-monophosphate reductase complexes revealed by high-resolution 31P field-cycling NMR relaxometry
Biochemistry
57
3146-3154
2018
Homo sapiens (Q9P2T1)
brenda
Sommerville, E.W.; Dalla Rosa, I.; Rosenberg, M.M.; Bruni, F.; Thompson, K.; Rocha, M.; Blakely, E.L.; He, L.; Falkous, G.; Schaefer, A.M.; Yu-Wai-Man, P.; Chinnery, P.F.; Hedstrom, L.; Spinazzola, A.; Taylor, R.W.; Gorman, G.S.
Identification of a novel heterozygous guanosine monophosphate reductase (GMPR) variant in a patient with a late-onset disorder of mitochondrial DNA maintenance
Clin. Genet.
97
276-286
2020
Homo sapiens (P36959)
brenda
Bairagya, H.R.; Tasneem, A.; Rai, G.P.; Reyaz, S.
Structural and dynamical impact of water molecules at substrate- or product-binding sites in human GMPR enzyme A study by molecular dynamics simulations
J. Phys. Chem. B
125
1351-1362
2021
Homo sapiens (P36959), Homo sapiens (Q9P2T1), Homo sapiens
brenda