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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
NADPH + H+ + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
-
?
additional information
?
-
enzyme nucleotide bindng analysis, nucleotide binding alters the quarternary structure of the enzyme, overview
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-
?
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
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
reductive deamination of GMP, the back conversion of IMP to GMP is highly unfavorable
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
GMP + NADPH + H+
IMP + NH3 + NADP+
-
-
-
?
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
-
the rate of the reverse reaction is 6% of the forward reaction
-
r
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
involved in salvage pathway of purine synthesis
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
GMP and IMP binding are thermodynamically favorable processes. Protonation and hydride transfer steps take place in the same transition state. Product release does not contribute to the rate-limiting step of the reaction
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
specific for GMP
-
ir
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
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
specific for GMP
-
ir
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
-
?
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
enzyme may play a role in brown fat response
-
?
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
-
specific for GMP
-
ir
NADPH + guanosine 5'-phosphate
NADP+ + inosine 5'-phosphate + NH3
-
enzyme is involved in interconversion of purine ribonucleotides
-
ir
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metabolism
the enzyme activity establishes a link between guanosine metabolism and RHOGTPase-dependent melanoma cell invasion
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
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
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
-
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
loss of the cystathionine-beta-synthase, CBS, domain may impair the catalytic activity of mutant lmgmprDELTACBS and/or cause a disruption of the protein structure
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
physiological function
enzyme GMPR modulates the concentration of intracellular guanosine in the pathogen
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
physiological function
the cystathionine-beta-synthase domains on the guanosine 5-monophosphate reductase regulates the enzymatic activity in response to guanylate nucleotide levels. Recombinant enzyme LmGMPR complements the DELTAguaC mutation in Escherichia coli strain H1174 lacking bacterial GMPR
physiological function
-
enzyme GMPR modulates the concentration of intracellular guanosine in the pathogen
-
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
additional information
LmGMPR subunits may adopt conformations with Trp121 differentially exposed to the aqueous environment, binding of ATP resulted in an emission spectrum with a lambdamax centered at 350 nm indicative of a conformational change that position Trp121 into a more solvent exposed environment
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Cloning of the Escherichia coli K-12 guaC gene following its transposition into the RP4:Mu cointegrate
Gene
40
141-143
1985
Escherichia coli
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Stephens, R.W.; Whittaker, V.K.
Calf thymus GMP reductase: control by XMP
Biochem. Biophys. Res. Commun.
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1973
Bos taurus
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Endo, T.; Uratani, B.; Freese, E.
Purine salvage pathways of Bacillus subtilis and effect of guanine on growth of GMP reductase mutants
J. Bacteriol.
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1983
Bacillus subtilis
brenda
Andrews, S.C.; Guest, J.R.
Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12
Biochem. J.
255
35-43
1988
Escherichia coli
brenda
Spector, T.; Jones, T.E.
Guanosine 5-monophosphate reductase from Leishmania donovani. A possible chemotherapeutic target
Biochem. Pharmacol.
31
3891-3897
1982
Leishmania donovani
brenda
Neuhard, J.; Nygaard, P.
Escherichia coli and Salmonella typhimurium cellular and molecular biology
American Society for Microbiology Washington (Neidhardt, F. C. , Ingraham, J. L. , Low, K. B. , Magasanik, B. , Schaechter, M. , Umbarger, E. , eds. )
1
445-473
1987
Salmonella enterica subsp. enterica serovar Typhimurium
-
brenda
Garber, B.B.; Jochimsen, B.U.; Gots, J.S.
Glutamine and related analogs regulate guanosine monophosphate reductase in Salmonella typhimurium
J. Bacteriol.
143
105-111
1980
Salmonella enterica subsp. enterica serovar Typhimurium
brenda
Mitchell, A.; Sin, I.L.; Finch, L.R.
Enzymes of purine metabolism in Mycoplasma mycoides subsp. mycoides
J. Bacteriol.
134
706-712
1978
Mycoplasma mycoides
brenda
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
Renart, M.F.; Renart, J.; Sillero, M.A.G.; Sillero, A.
Guanosine monophosphate reductase from Artemia salina: Inhibition by xanthosine monophosphate and activation by diguanosine tetraphosphate
Biochemistry
15
4962-4966
1976
Artemia salina
brenda
Renart, M.F.; Sillero, A.
GMP reductase in Artemia salina
Biochim. Biophys. Acta
341
178-186
1974
Artemia salina
brenda
Mackenzie, J.J.; Sorensen, L.B.
Guanosine 5-phosphate reductase of human erythrocytes
Biochim. Biophys. Acta
327
282-294
1973
Homo sapiens
brenda
Brox, L.W.; Hampton, A.
Inactivation of guanosine 5-phosphate reductase by 6-chloro-, 6-mercapto-, and 2-amino-6-mercapto-9-beta-D-ribofuranosylpurine 5-phosphates
Biochemistry
7
398-405
1968
Klebsiella aerogenes
brenda
Mager, J.; Magasanik, B.
Guanosine 5'-phosphate reductase and its role in the interconversion of purine nucleotides
J. Biol. Chem.
235
1474-1478
1960
Klebsiella aerogenes, Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
brenda
Salvatore, D.; Bartha, T.; Larsen, P.R.
The guanosine monophosphate reductase gene is conserved in rats and its expression increases rapidly in brown adipose tissue during cold exposure
J. Biol. Chem.
273
31092-31096
1998
Rattus norvegicus (Q9Z244)
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
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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
Mohamed Fahmy Gad El-Rab, S.; Abdel-Fattah Shoreit, A.; Fukumori, Y.
Effects of cadmium stress on growth, morphology, and protein expression in Rhodobacter capsulatus B10
Biosci. Biotechnol. Biochem.
70
2394-2402
2006
Rhodobacter capsulatus, Rhodobacter capsulatus B10
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
Martinelli, L.K.; Ducati, R.G.; Rosado, L.A.; Breda, A.; Selbach, B.P.; Santos, D.S.; Basso, L.A.
Recombinant Escherichia coli GMP reductase: kinetic, catalytic and chemical mechanisms, and thermodynamics of enzyme-ligand binary complex formation
Mol. Biosyst.
7
1289-1305
2011
Escherichia coli
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
Smith, S.; Boitz, J.; Chidambaram, E.S.; Chatterjee, A.; Ait-Tihyaty, M.; Ullman, B.; Jardim, A.
The cystathionine-beta-synthase domains on the guanosine 5'-monophosphate reductase and inosine 5'-monophosphate dehydrogenase enzymes from Leishmania regulate enzymatic activity in response to guanylate and adenylate nucleotide levels
Mol. Microbiol.
100
824-840
2016
Leishmania major (Q4QEB3)
brenda
Sarwono, A.E.Y.; Suganuma, K.; Mitsuhashi, S.; Okada, T.; Musinguzi, S.P.; Shigetomi, K.; Inoue, N.; Ubukata, M.
Identification and characterization of guanosine 5'-monophosphate reductase of Trypanosoma congolense as a drug target
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66
537-544
2017
Trypanosoma congolense (G0UMT0), Trypanosoma congolense, Trypanosoma congolense IL3000 (G0UMT0)
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
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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
Imamura, A.; Okada, T.; Mase, H.; Otani, T.; Kobayashi, T.; Tamura, M.; Kubata, B.K.; Inoue, K.; Rambo, R.P.; Uchiyama, S.; Ishii, K.; Nishimura, S.; Inui, T.
Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-beta-synthase domain
Nat. Commun.
11
1837
2020
Trypanosoma brucei, Trypanosoma brucei ILTat
brenda