ribose phosphate pyrophosphokinase


Summary: An enzyme that catalyzes the formation of phosphoribosyl pyrophosphate from ATP and ribose-5-phosphate. EC

Top Publications

  1. Hove Jensen B. Heterooligomeric phosphoribosyl diphosphate synthase of Saccharomyces cerevisiae: combinatorial expression of the five PRS genes in Escherichia coli. J Biol Chem. 2004;279:40345-50 pubmed
    ..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. ..
  2. Eriksen T, Kadziola A, Bentsen A, Harlow K, Larsen S. Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase. Nat Struct Biol. 2000;7:303-8 pubmed
    ..In addition to identifying residues important for binding substrates and effectors, the structures suggest a novel mode of allosteric regulation. ..
  3. Wang K, Vavassori S, Schweizer L, Schweizer M. Impaired PRPP-synthesizing capacity compromises cell integrity signalling in Saccharomyces cerevisiae. Microbiology. 2004;150:3327-39 pubmed
    ..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. ..
  4. Hernando Y, Parr A, Schweizer M. PRS5, the fifth member of the phosphoribosyl pyrophosphate synthetase gene family in Saccharomyces cerevisiae, is essential for cell viability in the absence of either PRS1 or PRS3. J Bacteriol. 1998;180:6404-7 pubmed
    ..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. ..
  5. Hove Jensen B, Harlow K, King C, Switzer R. Phosphoribosylpyrophosphate synthetase of Escherichia coli. Properties of the purified enzyme and primary structure of the prs gene. J Biol Chem. 1986;261:6765-71 pubmed
    ..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. ..
  6. Kim H, Sohn K, Shy M, Krajewski K, Hwang M, Park J, et al. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5). Am J Hum Genet. 2007;81:552-8 pubmed
  7. de Brouwer A, Williams K, Duley J, van Kuilenburg A, Nabuurs S, Egmont Petersen M, et al. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet. 2007;81:507-18 pubmed
    ..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. ..
  8. Kadziola A, Jepsen C, Johansson E, McGuire J, Larsen S, Hove Jensen B. Novel class III phosphoribosyl diphosphate synthase: structure and properties of the tetrameric, phosphate-activated, non-allosterically inhibited enzyme from Methanocaldococcus jannaschii. J Mol Biol. 2005;354:815-28 pubmed publisher
  9. Koslowsky S, Riegler H, Bergmuller E, Zrenner R. Higher biomass accumulation by increasing phosphoribosylpyrophosphate synthetase activity in Arabidopsis thaliana and Nicotiana tabacum. Plant Biotechnol J. 2008;6:281-94 pubmed
    ..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. ..

More Information


  1. Carter A, Narbad A, Pearson B, Beck K, Logghe M, Contreras R, et al. Phosphoribosylpyrophosphate synthetase (PRS): a new gene family in Saccharomyces cerevisiae. Yeast. 1994;10:1031-44 pubmed
    ..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. ..
  2. Vavassori S, Wang K, Schweizer L, Schweizer M. Ramifications of impaired PRPP synthesis in Saccharomyces cerevisiae. Biochem Soc Trans. 2005;33:1418-20 pubmed
    ..This approach provides insight into the co-ordination of different biological processes. ..
  3. Li S, Lu Y, Peng B, Ding J. Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site. Biochem J. 2007;401:39-47 pubmed
  4. Krath B, Hove Jensen B. Implications of secondary structure prediction and amino acid sequence comparison of class I and class II phosphoribosyl diphosphate synthases on catalysis, regulation, and quaternary structure. Protein Sci. 2001;10:2317-24 pubmed
    ..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. ..
  5. Becker M, Smith P, Taylor W, Mustafi R, Switzer R. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest. 1995;96:2133-41 pubmed
    ..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. ..
  6. Vavassori S, Wang K, Schweizer L, Schweizer M. In Saccharomyces cerevisiae, impaired PRPP synthesis is accompanied by valproate and Li+ sensitivity. Biochem Soc Trans. 2005;33:1154-7 pubmed
    ..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. ..
  7. Garcia Gil M, Pesi R, Perna S, Allegrini S, Giannecchini M, Camici M, et al. 5'-aminoimidazole-4-carboxamide riboside induces apoptosis in human neuroblastoma cells. Neuroscience. 2003;117:811-20 pubmed
    ..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...
  8. Ishizuka T, Ahmad I, Kita K, Sonoda T, Ishijima S, Sawa K, et al. The human phosphoribosylpyrophosphate synthetase-associated protein 39 gene (PRPSAP1) is located in the chromosome region 17q24-q25. Genomics. 1996;33:332-4 pubmed
  9. Yamada Y. [Hyperuricemia associated with inborn errors of purine metabolism: screening, enzymatic and genetic diagnosis]. Nihon Rinsho. 2003;61 Suppl 1:278-83 pubmed
  10. Yamaoka T, Itakura M. [Metabolism of purine nucleotides and the production of uric acid]. Nihon Rinsho. 1996;54:3188-94 pubmed
  11. Liu L, Liu J, Lu Y. Effects of Sheng-Mai injection on the PRPP synthetase activity in BFU-es and CFU-es from bone marrows of mice with benzene-induced aplastic anemia. Life Sci. 2001;69:1373-9 pubmed
    ..SMI can distinctly increase the reduced quantity of erythroid progenitor cells and promote rapid restoration of PRPP synthetase activity in CFU-Es of AA mice. ..
  12. Yamada Y, Yamada K, Nomura N, Yamano A, Kimura R, Tomida S, et al. Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked inborn errors of purine metabolism. Nucleosides Nucleotides Nucleic Acids. 2010;29:291-4 pubmed publisher
    ..In these four patients, we also performed molecular analysis of PRPS1, but no mutations in PRPP synthetase were found. ..
  13. Kita K, Ishizuka T, Ishijima S, Sonoda T, Tatibana M. A novel 39-kDa phosphoribosylpyrophosphate synthetase-associated protein of rat liver. Cloning, high sequence similarity to the catalytic subunits, and a negative regulatory role. J Biol Chem. 1994;269:8334-40 pubmed
    ..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. ..
  14. Sakakibara Y. Suppression of thermosensitive initiation of DNA replication in a dnaR mutant of Escherichia coli by a rifampin resistance mutation in the rpoB gene. J Bacteriol. 1995;177:733-7 pubmed
    ..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. ..
  15. Nagaya M, Aiba H, Mizuno T. A cyanobacterial gene encoding a protein with extensive homology to mammalian phosphoribosylpyrophosphate synthetase. Biosci Biotechnol Biochem. 1993;57:1958-9 pubmed
    ..We provide evidence that a cyanobacterium, Synechococcus sp., has a gene encoding a protein with striking homology to mammalian PRibPP synthetases. ..
  16. Hove Jensen B, Nygaard P. Phosphoribosylpyrophosphate synthetase of Escherichia coli, Identification of a mutant enzyme. Eur J Biochem. 1982;126:327-32 pubmed
    ..The mutation responsible for the altered PRib-PP synthetase was located in the purB-hemA region at 26 min on the recalibrated linkage map. ..
  17. Tang W, Li X, Zhu Z, Tong S, Li X, Zhang X, et al. Expression, purification, crystallization and preliminary X-ray diffraction analysis of human phosphoribosyl pyrophosphate synthetase 1 (PRS1). Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006;62:432-4 pubmed
    ..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. ..
  18. Shimizu R, Ji J, Kelsey E, Ohtsu K, Schnable P, Scanlon M. Tissue specificity and evolution of meristematic WOX3 function. Plant Physiol. 2009;149:841-50 pubmed publisher
  19. Ichida K. [Primary underproductive hypouricemia]. Nihon Rinsho. 2003;61 Suppl 1:364-7 pubmed
  20. Kawasugi K, Takeuchi F. [PRPP synthetase superactivity]. Nihon Rinsho. 2003;61 Suppl 1:284-7 pubmed
  21. Hernando Y, Carter A, Sickinger S, Schweizer M. Characterization of the promoter of PRS1 in Saccharomyces cerevisiae identifies three regions potentially involved in control of expression. J Bacteriol. 2001;183:795-9 pubmed
    ..Gel shift analysis confirmed the data. ..
  22. Nakano H, Goto S, Nakayashiki T, Inokuchi H. Temperature-sensitive mutations in various genes of Escherichia coli K12 can be suppressed by the ssrA gene for 10Sa RNA (tmRNA). Mol Genet Genomics. 2001;265:615-21 pubmed
    ..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. ..
  23. Becker M, Heidler S, Bell G, Seino S, Le Beau M, Westbrook C, et al. Cloning of cDNAs for human phosphoribosylpyrophosphate synthetases 1 and 2 and X chromosome localization of PRPS1 and PRPS2 genes. Genomics. 1990;8:555-61 pubmed
    ..Human HPRT and PRPS1 loci are not closely linked. Despite marked cDNA and deduced amino acid sequence homology, human PRS 1 and PRS 2 isoforms are encoded by genes widely separated on the X chromosome. ..
  24. Binley K, Radcliffe P, Trevethick J, Duffy K, Sudbery P. The yeast PRS3 gene is required for cell integrity, cell cycle arrest upon nutrient deprivation, ion homeostasis and the proper organization of the actin cytoskeleton. Yeast. 1999;15:1459-69 pubmed
    ..In the same colony-sectoring assay, an mpk1 allele was also recovered. Multicopy PRS3 rescued the caffeine sensitivity of this mpk1 allele. ..
  25. Ishijima S, Taira M, Tatibana M. Complete cDNA sequence of rat phosphoribosylpyrophosphate synthetase subunit I (PRS I). Nucleic Acids Res. 1989;17:8860 pubmed
  26. Iizasa T, Taira M, Shimada H, Tatibana M. Deduced amino acid sequence from human phosphoribosylpyrophosphate synthetase subunit II cDNA. Adv Exp Med Biol. 1989;253A:519-23 pubmed
  27. Roessler B, Nosal J, Smith P, Heidler S, Palella T, Switzer R, et al. Human X-linked phosphoribosylpyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. J Biol Chem. 1993;268:26476-81 pubmed
    ..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. ..
  28. He B, Choi K, Zalkin H. Regulation of Escherichia coli glnB, prsA, and speA by the purine repressor. J Bacteriol. 1993;175:3598-606 pubmed
    ..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. ..
  29. Sonoda T, Kita K, Ishijima S, Ishizuka T, Ahmad I, Tatibana M. Kinetic and regulatory properties of rat liver phosphoribosylpyrophosphate synthetase complex are partly distinct from those of isolated recombinant component catalytic subunits. J Biochem. 1997;122:635-40 pubmed
  30. Nyhan W. Inherited hyperuricemic disorders. Contrib Nephrol. 2005;147:22-34 pubmed
    ..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. ..
  31. Becker M, Kim M. Regulation of purine synthesis de novo in human fibroblasts by purine nucleotides and phosphoribosylpyrophosphate. J Biol Chem. 1987;262:14531-7 pubmed
    ..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. ..
  32. Nakamura T. [Historical review of gout and hyperuricemia investigations]. Nihon Rinsho. 2008;66:624-35 pubmed
    ..However, the mechanism in majority of the overproduction has not yet been clarified and is currently under investigation. ..
  33. Taira M, Iizasa T, Yamada K, Shimada H, Tatibana M. Tissue-differential expression of two distinct genes for phosphoribosyl pyrophosphate synthetase and existence of the testis-specific transcript. Biochim Biophys Acta. 1989;1007:203-8 pubmed
    ..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. ..
  34. Kaida A, Ariumi Y, Baba K, Matsubae M, Takao T, Shimotohno K. Identification of a novel p300-specific-associating protein, PRS1 (phosphoribosylpyrophosphate synthetase subunit 1). Biochem J. 2005;391:239-47 pubmed
    ..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. ..
  35. Post D, Switzer R, Hove Jensen B. The defective phosphoribosyl diphosphate synthase in a temperature-sensitive prs-2 mutant of Escherichia coli is compensated by increased enzyme synthesis. Microbiology. 1996;142 ( Pt 2):359-65 pubmed
    ..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. ..
  36. Hove Jensen B, Rosenkrantz T, Haldimann A, Wanner B. Escherichia coli phnN, encoding ribose 1,5-bisphosphokinase activity (phosphoribosyl diphosphate forming): dual role in phosphonate degradation and NAD biosynthesis pathways. J Bacteriol. 2003;185:2793-801 pubmed
  37. Ahmed M, Taylor W, Smith P, Becker M. Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. J Biol Chem. 1999;274:7482-8 pubmed
    ..The genetic basis of disordered PRPS1 transcription remains unresolved; normal- and patient-derived PRPS1s share nucleotide sequence identity at least 850 base pairs 5' to the consensus transcription initiation site. ..
  38. Sinha S, Smith J. The PRT protein family. Curr Opin Struct Biol. 2001;11:733-9 pubmed
    ..New crystal structures have revealed key elements of PRT protein function, as well as glimpses of how the fold has evolved to perform both catalytic and regulatory functions. ..
  39. Latham K, Patel B, Bautista F, Hawes S. Effects of X chromosome number and parental origin on X-linked gene expression in preimplantation mouse embryos. Biol Reprod. 2000;63:64-73 pubmed
    ..The results also indicate that early dosage compensation in preimplantation embryos may normally be reversible, thus providing flexibility to meet different developmental requirements of the embryonic and extraembryonic lineages. ..
  40. Sonoda T, Taira M, Ishijima S, Ishizuka T, Iizasa T, Tatibana M. Complete nucleotide sequence of human phosphoribosyl pyrophosphate synthetase subunit I (PRS I) cDNA and a comparison with human and rat PRPS gene families. J Biochem. 1991;109:361-4 pubmed
    ..Based on the evolutionary rate of amino acid substitution, the PRS I and II genes probably diverged about 760 million years ago. ..
  41. Katashima R, Iwahana H, Fujimura M, Yamaoka T, Ishizuka T, Tatibana M, et al. Molecular cloning of a human cDNA for the 41-kDa phosphoribosylpyrophosphate synthetase-associated protein. Biochim Biophys Acta. 1998;1396:245-50 pubmed
    ..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. ..
  42. Hove Jensen B, Bentsen A, Harlow K. Catalytic residues Lys197 and Arg199 of Bacillus subtilis phosphoribosyl diphosphate synthase. Alanine-scanning mutagenesis of the flexible catalytic loop. FEBS J. 2005;272:3631-9 pubmed
    ..The data presented show that Lys197 and Arg199 are important in stabilization of the transition state. ..
  43. Blacketer M, Madaule P, Myers A. The Saccharomyces cerevisiae mutation elm4-1 facilitates pseudohyphal differentiation and interacts with a deficiency in phosphoribosylpyrophosphate synthase activity to cause constitutive pseudohyphal growth. Mol Cell Biol. 1994;14:4671-81 pubmed
    ..Thus, the pps1-1 mutation may generate a nitrogen limitation signal, which when coupled with elm4-1 results in pseudohyphal growth even in rich medium. ..
  44. Xie G, Bonner C, Jensen R. Dynamic diversity of the tryptophan pathway in chlamydiae: reductive evolution and a novel operon for tryptophan recapture. Genome Biol. 2002;3:research0051 pubmed
    ..C. psittaci appears to have a novel mechanism for intercepting an early intermediate of tryptophan catabolism and recycling it back to tryptophan. In effect, a host-parasite metabolic mosaic has evolved for tryptophan recycling. ..
  45. Nilsson D, Hove Jensen B, Arnvig K. Primary structure of the tms and prs genes of Bacillus subtilis. Mol Gen Genet. 1989;218:565-71 pubmed
    ..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. ..
  46. Kita K, Otsuki T, Ishizuka T, Tatibana M. Rat liver phosphoribosyl pyrophosphate synthetase: existence of the purified enzyme as heterogeneous aggregates and identification of the catalytic subunit. J Biochem. 1989;105:736-41 pubmed
    ..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. ..
  47. Bower S, Harlow K, Switzer R, Hove Jensen B. Characterization of the Escherichia coli prsA1-encoded mutant phosphoribosylpyrophosphate synthetase identifies a divalent cation-nucleotide binding site. J Biol Chem. 1989;264:10287-91 pubmed
    ..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. ..
  48. Kian I, Etingof R. Purine biosynthesis de novo in bovine retina: purification and characterization of amidophosphoribosyl transferase and phosphoribosyl pyrophosphate synthetase. Biochemistry (Mosc). 1999;64:648-51 pubmed
    ..The sensitivity of the retinal PRPP synthetase to inhibition by ADP and AMP was significantly lower than that of the enzyme from the liver. ..
  49. Jimenez A, Santos M, Revuelta J. Phosphoribosyl pyrophosphate synthetase activity affects growth and riboflavin production in Ashbya gossypii. BMC Biotechnol. 2008;8:67 pubmed publisher
    ..It is shown that alterations in PRPP synthetase activity have pleiotropic effects on the fungal growth pattern and that an increase in PRPP synthetase enzymatic activity can be used to enhance riboflavin production in A. gossypii. ..
  50. Kawaguchi T, Veech R, Uyeda K. Regulation of energy metabolism in macrophages during hypoxia. Roles of fructose 2,6-bisphosphate and ribose 1,5-bisphosphate. J Biol Chem. 2001;276:28554-61 pubmed
    ..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. ..
  51. Kleineidam A, Vavassori S, Wang K, Schweizer L, Griac P, Schweizer M. Valproic acid- and lithium-sensitivity in prs mutants of Saccharomyces cerevisiae. Biochem Soc Trans. 2009;37:1115-20 pubmed publisher
    ..These studies on yeast PRPP synthetases bring together and expand the current theories for the mood-stabilizing effects of VPA and LiCl in bipolar disorder. ..
  52. Sonoda T, Ishizuka T, Ishijima S, Kita K, Ahmad I, Tatibana M. Rat liver phosphoribosylpyrophosphate synthetase is activated by free Mg2+ in a manner that overcomes its inhibition by nucleotides. Biochim Biophys Acta. 1998;1387:32-40 pubmed
    ..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. ..
  53. Kawasugi K, Takeuchi F. [PRPP synthetase deficiency]. Nihon Rinsho. 2003;61 Suppl 1:383-5 pubmed