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Information on EC 1.7.1.7 - GMP reductase and Organism(s) Homo sapiens
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1.7.1.7 GMP reductaseSpecify your search results
Word Map
- 1.7.1.7
- purine
- imp
-
salvage
- hypoxanthine
- impdhs
-
hypoxanthine-guanine
- adenylosuccinate
- medicine
- drug development
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
gmp reductase, gmpr2, guanosine monophosphate reductase, guanosine 5'-monophosphate reductase, tbgmpr, guanosine-5'-monophosphate reductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GMPR
GMPR2
Guanosine 5'-monophosphate oxidoreductase
-
-
-
-
guanosine 5'-monophosphate reductase
-
-
-
-
guanosine monophosphate reductase
guanylate reductase
-
-
-
-
NADPH:GMP oxidoreductase (deaminating)
-
-
-
-
reductase, guanylate
-
-
-
-
guanosine monophosphate reductase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
IMP + NH3 + NADP+ = GMP + NADPH + H+
mechanism: ordered sequential with GMP binding first
-
IMP + NH3 + NADP+ = GMP + NADPH + H+
catalytic reaction mechanism, overview. GMPR catalyzes two different chemical transformations at the same active site via two different cofactor conformations, analysis by subtesla high resolution field cycling NMR relaxometry
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reductive deamination
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
inosine-5'-phosphate:NADP+ oxidoreductase (aminating)
-
CAS REGISTRY NUMBER
COMMENTARY
9029-32-7
-
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
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
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
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
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the human enzyme is not activated in the presence of KCl instead of NaCl
additional information
the human enzyme is not activated in the presence of KCl instead of NaCl
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
mizoribine 5'-monophosphate
MZP, moderate inhibition; MZP, moderate inhibition
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
0.016
NADPH
wild type enzyme, with GMP as cosubstrate, at pH 7.8 and 25°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
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
-
pH 6: about 50% of activity at maximum, pH 9: about 70% of activity at maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expression of guanosine monophosphate reductase (GMPR), an enzyme involved in de novo biosynthesis of purine nucleotides, is downregulated in invasive stages of human melanoma. From 9 arbitrarily chosen human metastatic melanoma cell lines, GMPR is expressed in only one cell line
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
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
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). GMPR1_HUMAN
345
0
37419
Swiss-Prot
other Location (Reliability: 4)
GMPR2_HUMAN
348
0
37874
Swiss-Prot
other Location (Reliability: 2)
H0YNJ6_HUMAN
427
0
46938
TrEMBL
Mitochondrion (Reliability: 4)
Q6PKC0_HUMAN
409
0
45008
TrEMBL
other Location (Reliability: 2)
Q7Z527_HUMAN
350
0
38517
TrEMBL
other Location (Reliability: 2)
H0YLV5_HUMAN
333
0
35852
TrEMBL
Mitochondrion (Reliability: 4)
H0YMB3_HUMAN
315
0
33922
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C186A
site-directed mutagenesis, a catalytically inactive mutant, overexpression of GMPRC186A mutant at levels comparable to overexpression of wild-type GMPR does not affect invasion in of melanoma cells
D219A
the mutant shows reduced affinities for substrate and cofactor compared to the wild type enzyme
G183R
the variant 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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 2-mercaptoethanol, 6 months, less than 15% loss of activity after several rounds of freezing and thawing
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of wild-type and mutant enzymes in SK-Mel-103 melanoma cells
transfection of HL-60 leukemia cells, expressed in COS-7 cells as His-tag fusion protein
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of guanosine monophosphate reductase (GMPR), an enzyme involved in de novo biosynthesis of purine nucleotides, is downregulated in invasive stages of human melanoma
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
Mackenzie, J.J.; Sorensen, L.B.
Guanosine 5-phosphate reductase of human erythrocytes
Biochim. Biophys. Acta
327
282-294
1973
Homo sapiens
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
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
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
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
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
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)
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)
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)
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)
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
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