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GMP + NADPH + H+
IMP + NH3 + NADP+
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
-
-
?
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+
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+
-
-
-
?
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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5,5'-dithiobis(2-nitrobenzoate)
-
0.66 mM, 33% inhibition after 30 min
6-Chloro-9-beta-D-ribofuranosylpurine 5'-phosphate
-
0.01 mM, 80% inhibition after 40 min, 1 mM GMP protect
6-Chloropurine ribonucleotide
-
-
adenosine 2'-phosphate
-
-
ADP
-
2 mM, 85% inhibition
Fe2+
-
10 mM, more than 90% inhibition
iodoacetamide
-
progressive inhibition, 2 mM GMP protect
iodoacetate
-
progressive inhibition, 2 mM GMP protect
mizoribine 5'-monophosphate
p-mercuribenzoate
-
2 mM, complete inhibition, complete protection by 2 mM GSH
ribavirin 5'-monophosphate
RMP, competitive inhibition
XTP
0.05 mM, 50% inhibition
6-Thio-GMP

-
-
6-Thio-GMP
-
0.009 mM, 81% inhibition after 30 min
6-thio-IMP

-
-
6-thio-IMP
-
0.32 mM, 75% inhibition after 15 min
AMP

-
weak
AMP
-
2 mM, 56% inhibition
ATP

-
-
ATP
-
0.4 mM, 92% inhibition
ATP
-
no inhibition without Mg2+, MgATP: no inhibition at 0.010 mM-0.100 mM GMP, strong inhibition below 0.010 mM
Ca2+

-
10 mM, 54% inhibition
Ca2+
1 mM, 49% inhibition
Cu2+

-
-
Cu2+
1 mM, more than 90% inhibition
GTP

0.05 mM, 30% inhibition
IMP

-
1 mM, 10% inhibition, 2 mM, 20% inhibition
IMP
-
0.05 mM, 25% inhibition, competitive vs. GMP
IMP
competitive versus GMP
Mg2+

-
10 mM, more than 90% inhibition, 1 mM, 12% inhibition
mizoribine 5'-monophosphate

MZP, moderate inhibition; MZP, moderate inhibition
mizoribine 5'-monophosphate
MZP
Mycophenolic acid

competitive versus NADPH
Ni2+

-
-
Ni2+
1 mM, more than 90% inhibition
p-hydroxymercuribenzoate

-
-
p-hydroxymercuribenzoate
-
0.66 mM, 18% inhibition after 30 min
XMP

-
0.001 mM, more than 50% inhibition; GTP and diguanosine tetraphosphate counteract inhibition
XMP
-
0.0005 mM, 89% inhibition
XMP
-
competitive vs. GMP, noncompetitive vs. NADPH
XMP
0.05 mM, 99% inhibition
Zn2+

-
10 mM, more than 90% inhibition
Zn2+
1 mM, 86% inhibition
additional information

-
not inhibited by ATP
-
additional information
-
not inhibited by ATP
-
additional information
-
not inhibited by KCN
-
additional information
-
not inhibited by ATP
-
additional information
not inhibited by ATP
-
additional information
no inhibition by ribavirin 5'-monophosphate; no inhibition by ribavirin 5'-monophosphate
-
additional information
no inhibition by ribavirin 5'-monophosphate; no inhibition by ribavirin 5'-monophosphate
-
additional information
-
not inhibited by KCN
-
additional information
-
not inhibited by KCN
-
additional information
ribavirin acts as an anti-trypanosomal drug in vitro with IC50 = 0.0254 mM
-
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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
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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Calf thymus GMP reductase: control by XMP
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Bos taurus
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Purine salvage pathways of Bacillus subtilis and effect of guanine on growth of GMP reductase mutants
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Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12
Biochem. J.
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1988
Escherichia coli
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Spector, T.; Jones, T.E.
Guanosine 5-monophosphate reductase from Leishmania donovani. A possible chemotherapeutic target
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1982
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Escherichia coli and Salmonella typhimurium cellular and molecular biology
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Salmonella enterica subsp. enterica serovar Typhimurium
-
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Glutamine and related analogs regulate guanosine monophosphate reductase in Salmonella typhimurium
J. Bacteriol.
143
105-111
1980
Salmonella enterica subsp. enterica serovar Typhimurium
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Enzymes of purine metabolism in Mycoplasma mycoides subsp. mycoides
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Reaction mechanism and specificity of human GMP reductase. Substrates, inhibitors, activators, and inactivators
J. Biol. Chem.
254
2308-2315
1979
Homo sapiens
brenda
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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
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Guanosine 5'-phosphate reductase and its role in the interconversion of purine nucleotides
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1960
Klebsiella aerogenes, Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
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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
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Homo sapiens, Homo sapiens (Q9P2T1), no activity in Haemophilus influenzae, no activity in Methanocaldococcus jannaschii, no activity in Mycoplasma genitalium
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Purification, crystallization and preliminary X-ray studies of GMP reductase 2 from human
Acta Crystallogr. Sect. D
59
1109-1110
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Homo sapiens
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Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells
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Effects of cadmium stress on growth, morphology, and protein expression in Rhodobacter capsulatus B10
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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
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355
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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
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7
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Escherichia coli
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A purine nucleotide biosynthesis enzyme guanosine monophosphate reductase is a suppressor of melanoma invasion
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5
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2013
Homo sapiens (P36959), Homo sapiens
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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
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291
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Homo sapiens (Q9P2T1)
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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
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Leishmania major (Q4QEB3)
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Identification and characterization of guanosine 5'-monophosphate reductase of Trypanosoma congolense as a drug target
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66
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10
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