ribose phosphate pyrophosphokinase

..To replenish low levels of purines, treatment with S-adenosylmethionine theoretically could have therapeutic efficacy, and a clinical trial involving the two affected Australian brothers is currently underway...

..Transcription terminated approximately 35 nucleotides downstream from the UAA translation stop codon, within a Thy-rich region following an inverted repeat sequence, indicative of an rho-independent transcription terminator...

..subtilis enzyme show little conservation in the spinach enzyme. In contrast, residues of the active site of B. subtilis PRPP synthase show extensive conservation in spinach PRPP synthase isozyme 4...

..It is postulated that Prs polypeptides play a significant role in the remodelling of the cell wall and may have a direct involvement in cell integrity signalling...

..The activity of PRPP synthases containing subunits 1 and 3 or subunits 1, 2, and 5 was found to be dependent on Pi, to be temperature-sensitive, and inhibited by ADP...

..The functional consequences of these mutations provide a tenable basis for the enhanced production of phosphoribosylpyrophosphate, purine nucleotides, and uric acid that are the biochemical hallmarks of PRS superactivity...

..Interference with the complement of PRS genes in S. cerevisiae has far-reaching consequences for yeast physiology and has uncovered unexpected metabolic links including cell wall integrity and phospholipid metabolism...

..However, simultaneous deletion of PRS1 and PRS5 or PRS3 and PRS5 rendered the strains inviable, which implies that PRS5 plays an important role in the maintenance of PRS function in S. cerevisiae...

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..This approach provides insight into the co-ordination of different biological processes...

..The results presented here suggest that the presence of this NHR is not detrimental to the function of the gene. To date the possibility of protein splicing can be neither proven nor disputed...

..This study provides evidence that the supply of PRPP co-limits growth rates, and has obvious implications for biotechnological strategies aiming to increase plant biomass as an alternative renewable energy source...

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..In addition to identifying residues important for binding substrates and effectors, the structures suggest a novel mode of allosteric regulation...

..We also mention purine metabolism disorders and their clinical consequences. The literature is fragmentary because studies have concentrated only on selected aspects of purine metabolism; hence the need for a synthetic approach...

..The availability of the different complexes should allow questions regarding the molecular mechanisms of catalysis and allostery in PRPP synthetase to be addressed...

..tuberculosis, and the tuberculosis drug ethambutol inhibits other steps in arabinan biosynthesis. Thus the Rv3806c-encoded enzyme appears to be a good target for the development of new tuberculosis drugs...

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..This is the first reported instance of PRS overactivity in which the propositus and sole affected family member is a woman...

..Here, regulation of purine biosynthesis pathway and relevant mechanisms are discussed. Genetic mechanisms for urate overproduction, dietary effects on urate amount and new drug therapy inhibiting urate production are also discussed...

..However, the mechanism in majority of the overproduction has not yet been clarified and is currently under investigation...

..These will no doubt expand our understanding of the pathogenesis of these disorders and provide innovative therapeutic approaches...

..6) We propose that MgGDP binds to a regulatory site of PRS I and PRS II and MgADP to the substrate MgATP site and also the regulatory site. The allosteric interaction of the regulatory site and the Mg2+ binding site is also considered...

..These results imply a functional role for at least two of the identified amino acid residues...

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..This strongly indicates that the binding of both substrates must lead to a stabilized conformation of the loop region, which remains unresolved in the known PRPPsase complex structures...

..The data presented show that Lys197 and Arg199 are important in stabilization of the transition state...

..The results indicated two- to threefold repression of these genes by purR. Coregulation by purR provides evidence that expands the pur regulon to include glnB, prsA, and speA. These genes have functions related to nucleotide metabolism...

..Inhibition of rPRS I and rPRS II by 0.3 mM ADP was 87 and 54%, respectively, and inhibition by 1 mM GDP was 93 and 24%, respectively. rPRS II was 180-fold more sensitive than rPRS I to heat inactivation at 49 degrees C...

..I propose that the dnaR product has a key role in transcriptional activation of the replication origin for the dnaA-dependent initiation of DNA replication...

..Transcripts of 2.3 and 3.7 kilobases were detected in YS cells and rat liver by Northern blot analysis, using PRS I and II cDNAs respectively, as probes. In the liver, the expression of both genes increased after partial hepatectomy...

..The contribution of each mutation to the phenotype of the mutant has been evaluated...

..The deduced Tms amino acid sequence was found to be 43% similar to the deduced amino acid sequence of ecourfl, a gene of E. coli with unknown function...

..2, b = 152.6, c = 149.3 A. The crystals diffract to a maximum resolution of 3.3 A and a complete data set to 3.5 A resolution was collected and analysed...

..pneumoniae. This crucial addition to the set of completed Chlamydiaceae genome sequences is enabling dissection of the roles played by niche-specific genes in these important bacterial pathogens...

..These genes are useful markers for elucidating the sexualization process...

..PRS2 mRNA levels increased twofold in roots and shoots of P-starved plants, while PRS3 was constitutively-expressed. PRS3 may play a novel role in providing PRPP to cellular metabolism under low P availability...

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..This global approach can provide a better understanding of S. pneumoniae adaptation to its human host and a clue for its pathogenicity...

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..C., unpublished data)...

..The spontaneous mutant I-9m harboring only pMWKQ and I-9m harboring both pMWKQ and pSTVDA (a plasmid having the desensitized-prs) accumulated 6.7 g/l and 7.5 g/l inosine, respectively, from 40 g/l glucose in a 3-d culture...

..In conclusion, our results provide valuable information for further understanding of the adipogenic process...

..The industrial production of this vitamin using the fungus Ashbya gossypii is an important biotechnological process that is strongly influenced by substrate availability...

..Each solution consists of a set of predicted values for metabolites, initial substrates and enzyme activities, which describe a biologically acceptable steady state of the system that shifts the pathologic state towards a healthy state...

..caldolyticus enzyme based on homology modelling with the structure of B. subtilis 5-phospho-alpha-D-ribosyl 1-diphosphate synthase shows 92% of the amino acid differences to be on solvent exposed surfaces in the hexameric structure...

..846, c = 61.857 angstroms, assuming two molecules in the asymmetric unit and a volume-to-weight ratio of 2.4 angstroms3 Da(-1), which was consistent with the result calculated from the self-rotation function...

..The mechanism producing increased mRNA is, however, not elucidated. The Japanese case has been found to be caused by the second mechanism...

..The undersecretion disorders are autosomal dominantly inherited and are heterogeneous. A major number of these patients result from mutations in the gene that codes for uromodulin. Treatment is with allopurinol...

..Contrary to standard models, we find no increased frequency of intron loss toward the 3' ends of genes. Thus, recent intron dynamics do not support a model whereby 5' intron positional bias is generated solely by 3'-biased intron loss...

..Based on these results, we propose that PAP39, the major component of PAPs, plays a negative regulatory role in PRPP synthesis and hence is an important factor controlling nucleotide syntheses in general...

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..Derepression of the prs gene upon pyrimidine starvation was shown to be due to an increase in the amount of message originating from the promoter P2...

..Further studies on these components and their interaction are expected to reveal various mechanisms governing mammalian PRPP synthetase...

..C. 2.7.6.1) activity in the human erythrocytes and that the biosynthetic pathways are active in immobilized cells at 37 degrees C. (5) The rates of accumulation of 2,3-DPG and phosphomonoesters (PME) appeared to be strongly correlated...

..Our data suggest that the mutant harbors a mutation in the structural gene for PRib-PP synthetase. The mutation responsible for the altered PRib-PP synthetase was located in the purB-hemA region at 26 min on the recalibrated linkage map...

..By deletion analysis and by cloning fragments of this leader sequence in a galK expression vector it was found to contain the prs promoter as well as a potential transcription termination site...

..The S. typhimurium leader contains a 115-base-pair insert relative to the E. coli leader. The insert appears to have no functional significance...

..5) The amino acid composition of the 34-kDa subunit and the amino acid sequences of its N-terminal region and of two tryptic peptides were determined. The results are in accord with the results of cDNA analyses...

..This amino acid homology seems to be the highest so far reported for enzymes involved in nucleotide metabolism and glycolysis. The highly conserved structure may be required for unique catalysis and rigid regulation of this enzyme...

..In the testis, an additional PRPS1-related transcript of 1.4 kb was noted in rats, mice and humans. This transcript may belong to a group of testis-specific gene expressions or functions...

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..3) Activation of amido PRT by PP-Rib-P is nearly maximal at base line in fibroblasts with regulatory defects in PP-Rib-P synthetase...

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..In lymphoblasts, however, expression of this alteration is attenuated, explaining the absence of phenotypic expression of PRS catalytic superactivity in these cells...

..05) in gerbils fed all diets containing isoflavones. Induction of these two mRNA by soy may be due to the aryl hydrocarbon receptor element in the promoter region of both genes...

..Considering the fact that ssrA-suppressible mutants could be isolated as temperature-sensitive mutants with mutations in different genes, it seems evident that trans-translation can occur on mRNA that is not lacking its stop codon...

..Our results raise the intriguing clue that the neurotoxic effect of AICA riboside on the developing brain might contribute to the neurological manifestations of syndromes related to purine dismetabolisms...

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..The fact that Deltaprs1 and Deltaprs3 are hypersensitive to caffeine and unable to recover from exposure to it as judged by the release of alkaline phosphatase points to a possible link between Prs and the maintenance of cell integrity...

..In the same colony-sectoring assay, an mpk1 allele was also recovered. Multicopy PRS3 rescued the caffeine sensitivity of this mpk1 allele...

..The sensitivity of the retinal PRPP synthetase to inhibition by ADP and AMP was significantly lower than that of the enzyme from the liver...

..Southern blot analysis suggested that the PAP41 gene exists as a single copy in the human genome. The single PAP41 mRNA of about 2.1 kb was shown to be present in five human cell lines by Northern blot analysis...

..Sequencing of the mutant prs gene of TS101 showed that residues 215, cysteine, in the encoded protein had been changed to tyrosine. That such a mutant exists suggests that 10Sa RNA associate with the prs gene product in a functional way...

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..In cells harbouring both mutations, the C --> T mutation appeared to compensate for the G --> A mutation by increasing the amount of a partially defective enzyme at the permissive temperature...

..These data suggest that the activation of the above enzymes was mediated by protein kinase C acting via activation of phosphatidylinositol specific phospholipase C in the macrophages during hypoxia...

..The synthesis of PRibPP is catalysed by a ubiquitous PRibPP synthetase in many organisms. We provide evidence that a cyanobacterium, Synechococcus sp., has a gene encoding a protein with striking homology to mammalian PRibPP synthetases...

..It has been previously proposed that a divalent cation binds to PRPP synthetase and serves as a bridge to the alpha-phosphate of ATP and AMP at the active site. The prsA1 mutation appears to alter this divalent cation site...

..1 micromol (min x mg of protein)(-1). The enzyme has an absolute requirement for magnesium ions, and maximal activity is obtained at 40 degrees C at pH 7.6...

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..This is the first report to demonstrate the existence of a p300 KIX-domain-specific-interacting protein that does not interact with CBP. Thus p300 may play a role in the regulation of DNA synthesis through interactions with PRS1...

..A comparison of the promoter region for PRPS1 with those of other housekeeping genes revealed a homology resembling that of the beta-actin gene...

..Normal, N. B., and S. M. PRS1 cDNAs were introduced into Escherichia coli BL21 (DE3)/pLyS, and recombinant N. B. and S. M. PRS1s showed the purine nucleotide feedback resistance phenotypes characteristic of PRS from patients' cells...