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At least 19 recordsLinked to original sources
PubMed2002

NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression, purification, and kinetic properties.

GMP reductase (EC 1.6.6.8) is the only known metabolic step by which guanine nucleotides can be converted to the pivotal precursor of both adenine and guanine nucleotides. Human GMP reductase has been previously partially purified from erythrocytes and a chromosome 6-linked cDNA has been identified to correspond for encoding human GMP reductase. Here, we reported a distinct cDNA for human GMP reductase isoenzyme isolated from a human fetal brain library, and the GenBank accession number is AF419346. The deduced protein shows 90% identity with human GMP reductase reported (named GMPR1 compared with GMPR2 of this paper) and 69% with E. coli GMP reductase. Comparison of GMPR2 cDNA sequence with human genome indicates the corresponding gene spans about 6.6kb on chromosome 14, which encodes 348 amino acid residues. Northern hybridization analysis indicates a differential and disproportionate expression of mRNAs for GMPR1 and GMPR2, suggesting the existence of distinct molecular species of GMP reductase in human. The apparent Km of GMPR2 for NADPH and GMP are 26.6 and 17.4 microM, respectively. This is the first report suggesting the existence of two distinct types of human GMP reductase molecular species, which can be used to explain the bimodal saturation curve noted with the purified human erythrocyte GMP reductase.

Amino Acid Sequence↗
PubMed2003

Purification, crystallization and preliminary X-ray studies of GMP reductase 2 from human.

GMP reductase 2 from human has been expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P3(2)21, with unit-cell parameters a = b = 110.6, c = 209.8 A, alpha = beta = 90, gamma = 120 degrees. Diffraction data were collected to 3.0 A with a completeness of 100% (100% for the last shell), an R(merge) value of 0.089 (0.189) and an I/sigma(I) value of 7.3 (3.2).

Crystallization↗
PubMed1988

Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12.

(1) The nucleotide sequence of a 1991 bp segment of DNA that expresses the GMP reductase (guaC) gene of Escherichia coli K12 was determined. (2) This gene comprises 1038 bp, 346 codons (including the initiation codon but excluding the termination codon), and it encodes a polypeptide of Mr 37,437 which is in good agreement with previous maxicell studies. (3) The sequence contains a putative promoter 102 bp upstream of the translational start codon, and this is immediately followed by a (G + C)-rich discriminator sequence suggesting that guaC expression may be under stringent control (4) The GMP reductase exhibits a high degree of sequence identity (34%) with IMP dehydrogenase (the guaB gene product) indicative of a close evolutionary relationship between the salvage pathway and the biosynthetic enzymes, GMP reductase and IMP dehydrogenase, respectively. (5) A single conserved cysteine residue, possibly involved in IMP binding to IMP dehydrogenase, was located within a region that possesses some of the features of a nucleotide binding site. (6) The IMP dehydrogenase polypeptide contains an internal segment of 123 amino acid residues that has no counterpart in GMP reductase and may represent an independent folding domain flanked by (alanine + glycine)-rich interdomain linkers.

Base Sequence↗
PubMed1984

Monophosphates of formycin B and allopurinol riboside. Interactions with leishmanial and mammalian succino-AMP synthetase and GMP reductase.

Formycin B 5'-monophosphate (Form B-MP) and allopurinol riboside 5'-monophosphate ( HPPR -MP) are isomers of IMP that are metabolically produced when Leishmania spp. are incubated with the antileishmanial agents formycin B and allopurinol or allopurinol riboside. The interactions of Form B-MP with succino -AMP synthetase and GMP reductase from both leishmanial and mammalian sources were compared with the data of earlier studies with HPPR -MP. Both analogs could substitute for IMP as a substrate for succino -AMP synthetase isolated from Leishmania donovani. The V'max values of Form B-MP and HPPR -MP were about 1% of the V'max of IMP. Only Form B-MP (and not HPPR -MP) could serve as an alternative substrate for mammalian succino -AMP synthetase. The V'max of Form B-MP was 40% that of IMP. The corresponding analogs of AMP, ADP and ATP were produced when Formycin B was incubated with mouse L cells. The Formycin A residue was incorporated into the cellular RNA. The amount of Formycin A-TP produced (relative to ATP) in mouse L cells was considerably less than that produced in Leishmania spp. Both Form B-MP and HPPR -MP were inhibitors of partially purified GMP reductase from L. donovani. The binding of Form B-MP and HPPR -MP to human GMP reductase was 40- and 100-fold weaker, respectively, than the binding to leishmanial GMP reductase. Pretreatment of promastigotes of L. donovani with either allopurinol or Formycin B resulted in greater than 95% reduction of the incorporation of the radiolabel from [14C]xanthine into ATP and greater than 80% reduction of the incorporation of the label into GTP. The HPPR -MP and Form B-MP present in these cells may have inhibited the leishmanial succino -AMP synthetase and GMP reductase. The analogs had little or no effect on the pool sizes of ATP and GTP of either mouse L cells or L. donovani.

Adenylosuccinate Synthase↗
PubMedDate not supplied

Reciprocal alterations of GMP reductase and IMP dehydrogenase activities during differentiation in HL-60 leukemia cells.

The study was undertaken to elucidate the regulatory roles of GMP reductase (GMPR) and IMP dehydrogenase (IMPDH) on purine interconversion during differentiation. Treatment of HL-60 cells with retinoic acid (1 microM) induced granulocytic differentiation which was accompanied with a 2.4-fold increase in GMPR and 55% decrease in IMPDH activities. Maturation induced by 12-O-tetradecanoylphorbol 13-acetate or dimethylsulfoxide was also associated with similar reciprocal alterations. Incubation with guanosine (200 microM), which expands the guanine nucleotide pool, elevated GMPR (1.9-fold) and decreased IMPDH (73%) activities. The synchronous and opposing alterations in GMPR and IMPDH activities should amplify the metabolic response due to differentiation or guanylate pool expansion.

Adenine Nucleotides↗
PubMedDate not supplied

[Characteristics of purine nucleotide metabolism and GMP-reductase activity in chicken tissues].

The [3H]guanosine and [3H]guanine label is shown to be distributed unevenly in the purine components of chicken tissues. 60 min after isotope administration about 80% of radioactivity is localized in xanthine and uric acid in the liver and duodenum, that agrees with high activity of purine nucleoside phosphorylase (EC 2.4.2.1) and guanine deaminase (EC 3.5.4.3). At the same time over 50% of label is found in the spleen in adenine nucleotides of the pool, RNA as well as in hypoxanthine and only 20% in oxypurines. Such a distribution of the label is in direct correlation with the activity of GMP-reductase (EC 1.6.6.8) catalyzing the reduction deamination of GMP in IMP.

Animals↗
PubMed1983

Purine salvage pathways of Bacillus subtilis and effect of guanine on growth of GMP reductase mutants.

We have isolated numerous mutants containing mutations in the salvage pathways of purine synthesis. The mutations cause deficiencies in adenine phosphoribosyltransferase (adeF), in hypoxanthine-guanine phosphoribosyltransferase (guaF), in adenine deaminase (adeC), in inosine-guanosine phosphorylase, (guaP), and in GMP reductase (guaC). The physiological properties of mutants containing one or more of these mutations and corresponding enzyme measurements have been used to derive a metabolic chart of the purine salvage pathway of Bacillus subtilis.

Bacillus subtilis↗
PubMed2003

[GMP reductase].

Explore the source record for details and available documents.

Adenosine Triphosphate↗
PubMed1975

Regulation of GMP reductase in Salmonella typhimurium.

The levels of guanosine 5'-phosphate reductase (EC 1.6.6.8) in Salmonella typhimurium appear to be modulated by changes in the ratio of the adenine and guanine nucleotide pools. Alterations of this ratio may be induced by high levels of guanosine in the culture medium or by genetic lesions in one of several purine interconversion enzymes, such as pur A or pur B mutants. The induction of the reductase requires transcription and translation processes and, in contrast to earlier observation with Escherichia coli, is not dependent on cyclic adenosine 3',5'-phosphate or the cyclic adenosine 3',5'-phosphate receptor protein.

Cyclic AMP↗
PubMed1991

Genomic structure and expression of human guanosine monophosphate reductase.

In vitro translation in the rabbit reticulocyte system and transient expression in Cos7 cells were performed to characterize the protein encoded by a chromosome 6-linked human cDNA clone, whose nucleotide sequence is homologous to that of Escherichia coli guanosine monophosphate reductase (GMP reductase) cDNA. The molecular weight of the peptide produced by the cDNA was about 37,000 Dalton, and the protein produced in the Cos7 cells exhibited GMP reductase activity, substantiating that the cDNA is for human GMP reductase. The corresponding genomic clones were obtained from two human genomic libraries. The gene spans about 50 kb and is composed of 9 exons, which encode 345 amino acid residues. Organization of exons and introns was established by DNA sequencing of each exon and splicing junctions. The gene contains two potential SpI binding sites within exon 1, and a functional atypical polyadenylation signal in exon 9.

Base Sequence↗
PubMed1978

Enzymes of purine metabolism in Mycoplasma mycoides subsp. mycoides.

The major pathways of ribonucleotide biosynthesis in Mycoplasma mycoides subsp. mycoides were proposed previously from studies of its usage of radioactive purines and pyrimidines. To interpret more fully the pattern of purine usage, we have assayed cell-free extracts of this organism for several enzymes associated with the salvage synthesis of purine nucleotides. M. mycoides possessed phosphoribosyltransferases for adenine, guanine, and hypoxanthine, purine nucleoside phosphorylase, GMP reductase, GMP kinase, adenylosuccinate synthetase, and adenylosuccinate lyase. Purine nucleoside kinase and adenosine deaminase were not detected. Examination of kinetic properties and regulation of some of the above enzymes revealed differences between M. mycoides and Escherichia coli. Most notable of these were the greater susceptibility of the enzymes from M. mycoides to inhibition by nucleotides and the more widespread involvement of GMP as an inhibitor. Observations on enzyme activities in vitro allow an adequate explanation of the capacity of guanine to provide M. mycoides with its full requirement for purine nucleotides.

Adenosine Monophosphate↗