Mammalian phosphoribosyl-pyrophosphate synthetase

Tatibana, Masamiti; Kita, K; Taira, Masanori; Ishijima, Sumio; Sonoda, Tomoko; Ishizuka, Toshiharu; Iizasa, Taizo; Ahmad, Imtiaz

doi:10.1016/0065-2571(94)00017-w

Cited by 41 publications

(27 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human and rat PRPP synthases also belong to the class I PRPP synthases, and as such their properties resemble the microbial class I PRPP synthases with respect to their restricted diphosphoryl donor capacity (ATP and dATP) and allosteric regulation by P i and ADP (18,20). The amino acid sequence identity among the three human PRPP synthase isozymes is 91% to 95%, whereas the identities of B. subtilis PRPP synthase and the three human isozymes are 45% or 46%.…”

Section: Class I Prpp Synthasesmentioning

confidence: 99%

“…In mammals, PRPP synthase polypeptides with an insertion have been designated PRPP synthase-associated proteins, or PAP. The descriptions below for each type of PRPP synthase and PAP complement previously published reviews (18,20).…”

Section: Class I Prpp Synthasesmentioning

confidence: 99%

“…For example, the overall identity of PRPP synthase amino acid sequences of E. coli and humans is 47% (20), and that of PRPP synthases of E. coli and the Gram-positive organism Bacillus subtilis is 51% (43). In addition, a 15-amino-acid sequence is highly conserved among PRPP synthase and adenine phosphoribosyltransferase (44,45).…”

Section: Classification and Properties Of Prpp Synthasesmentioning

confidence: 99%

See 2 more Smart Citations

Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance

Hove‐Jensen

Andersen

Kilstrup

et al. 2017

Microbiol Mol Biol Rev

168

187

View full text Add to dashboard Cite

SUMMARY Phosphoribosyl diphosphate (PRPP) is an important intermediate in cellular metabolism. PRPP is synthesized by PRPP synthase, as follows: ribose 5-phosphate + ATP → PRPP + AMP. PRPP is ubiquitously found in living organisms and is used in substitution reactions with the formation of glycosidic bonds. PRPP is utilized in the biosynthesis of purine and pyrimidine nucleotides, the amino acids histidine and tryptophan, the cofactors NAD and tetrahydromethanopterin, arabinosyl monophosphodecaprenol, and certain aminoglycoside antibiotics. The participation of PRPP in each of these metabolic pathways is reviewed. Central to the metabolism of PRPP is PRPP synthase, which has been studied from all kingdoms of life by classical mechanistic procedures. The results of these analyses are unified with recent progress in molecular enzymology and the elucidation of the three-dimensional structures of PRPP synthases from eubacteria, archaea, and humans. The structures and mechanisms of catalysis of the five diphosphoryltransferases are compared, as are those of selected enzymes of diphosphoryl transfer, phosphoryl transfer, and nucleotidyl transfer reactions. PRPP is used as a substrate by a large number phosphoribosyltransferases. The protein structures and reaction mechanisms of these phosphoribosyltransferases vary and demonstrate the versatility of PRPP as an intermediate in cellular physiology. PRPP synthases appear to have originated from a phosphoribosyltransferase during evolution, as demonstrated by phylogenetic analysis. PRPP, furthermore, is an effector molecule of purine and pyrimidine nucleotide biosynthesis, either by binding to PurR or PyrR regulatory proteins or as an allosteric activator of carbamoylphosphate synthetase. Genetic analyses have disclosed a number of mutants altered in the PRPP synthase-specifying genes in humans as well as bacterial species.

show abstract

Section: Class I Prpp Synthasesmentioning

confidence: 99%

Section: Class I Prpp Synthasesmentioning

confidence: 99%

Section: Classification and Properties Of Prpp Synthasesmentioning

confidence: 99%

See 1 more Smart Citation

Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance

Hove‐Jensen

Andersen

Kilstrup

et al. 2017

Microbiol Mol Biol Rev

168

187

View full text Add to dashboard Cite

show abstract

“…In other organisms PRS has been shown to be a multimeric complex of varying composition. For example the rat liver enzyme exists in an aggregate form composed of 34-kDa (PRSI and PRSII), 39-kDa (PAP39), and 41-kDa (PAP41) subunits in a ratio of 20:5:8:1 (55). In rubber tree latex the enzyme seems to be a tetramer (56), although the crystal structure of the Bacillus subtilis PRS has shown it to be hexameric (57) and in Salmonella typhimurium the smallest active form of PRS may be pentameric (58).…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis and Enzyme Activity Suggest the Existence of More Than One Minimal Functional Unit Capable of Synthesizing Phosphoribosyl Pyrophosphate in Saccharomyces cerevisiae

Hernando¹,

Carter²,

Parr³

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

The PRS gene family in Saccharomyces cerevisiae consists of five genes each capable of encoding a 5-phosphoribosyl-1(␣)-pyrophosphate synthetase polypeptide. To gain insight into the functional organization of this gene family we have constructed a collection of strains containing all possible combinations of disruptions in the five PRS genes. Phenotypically these deletant strains can be classified into three groups: (i) a lethal phenotype that corresponds to strains containing a double disruption in PRS2 and PRS4 in combination with a disruption in either PRS1 or PRS3; simultaneous deletion of PRS1 and PRS5 or PRS3 and PRS5 are also lethal combinations; (ii) a second phenotype that is encountered in strains containing disruptions in PRS1 and PRS3 together or in combination with any of the other PRS genes manifests itself as a reduction in growth rate, enzyme activity, and nucleotide content; (iii) a third phenotype that corresponds to strains that, although affected in their phosphoribosyl pyrophosphate-synthesizing ability, are unimpaired for growth and have nucleotide profiles virtually the same as the wild type. Deletions of PRS2, PRS4, and PRS5 or combinations thereof cause this phenotype. These results suggest that the polypeptides encoded by the members of the PRS gene family may be organized into two functional entities. Evidence that these polypeptides interact with each other in vivo was obtained using the yeast twohybrid system. Specifically PRS1 and PRS3 polypeptides interact strongly with each other, and there are significant interactions between the PRS5 polypeptide and either the PRS2 or PRS4 polypeptides. These data suggest that yeast phosphoribosyl pyrophosphate synthetase exists in vivo as multimeric complex(es).The enzyme 5-phosphoribosyl-1(␣)-pyrophosphate synthetase (ATP:D-ribose-5-phosphate pyrophosphotransferase; EC 2.7.6.1) (PRS) 1 catalyzes the reaction at a key junction in intermediary metabolism. PRS transfers the pyrophosphate moiety released from ATP to ribose-5-phosphate, thus giving rise to phosphoribosyl-pyrophosphate (PRPP) (1), and the enzyme therefore directs ribose-5-phosphate from energy generated by the pentose phosphate pathway to the important biosynthetic intermediate PRPP. PRPP is a precursor for the production of purine, pyrimidine, and pyridine nucleotides and the amino acids histidine and tryptophan (2). PRPP is required for both the de novo and the salvage pathways of nucleotide metabolism (3). It has been shown that in Mycobacterium spp. PRPP is also required for the biosynthesis of polyprenylphosphate pentoses that contribute to the arabinosyl residues of the cell wall (4).PRS genes have been cloned and sequenced from a variety of organisms; bacteria (5-9), mycoplasma (10), and protozoa (11) each contain apparently one PRS gene. In nematodes (12, 13) and the yeast Schizosaccharomyces pombe (14, 15) two PRS genes have been found so far, whereas in Spinacia oleracea four PRS cDNAs have been identified (16). PRS genes have also been cloned in rat (17-20) and human (21...

show abstract

“…This compound shows enzymatic inhibitory activity against the enzyme 5-phosphoribosyl R-1-pyrophosphate (PRPP) synthetase [221][222][223] with values [224] of 186 M (human type PRPP synthetase) and of 3811 mM (Bacillus subtilis PRPP synthetase). The enzyme PRPP synthetase converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP) (Scheme 18).…”

Section: Biological Activity Of Carbafuranosesmentioning

confidence: 99%

Biosynthesis and Biological Activity of Carbasugars

Roscales

Plumet

2016

International Journal of Carbohydrate Chemistry

View full text Add to dashboard Cite

The first synthesis of carbasugars, compounds in which the ring oxygen of a monosaccharide had been replaced by a methylene moiety, was described in 1966 by Professor G. E. McCasland's group. Seven years later, the first true natural carbasugar (5a-carba-R-D-galactopyranose) was isolated from a fermentation broth of Streptomyces sp. MA-4145. In the following decades, the chemistry and biology of carbasugars have been extensively studied. Most of these compounds show interesting biological properties, especially enzymatic inhibitory activities, and, in consequence, an important number of analogues have also been prepared in the search for improved biological activities. The aim of this review is to give coverage on the progress made in two important aspects of these compounds: the elucidation of their biosynthesis and the consideration of their biological properties, including the extensively studied carbapyranoses as well as the much less studied carbafuranoses.

show abstract

Mammalian phosphoribosyl-pyrophosphate synthetase

Cited by 41 publications

References 53 publications

Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance

Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance

Genetic Analysis and Enzyme Activity Suggest the Existence of More Than One Minimal Functional Unit Capable of Synthesizing Phosphoribosyl Pyrophosphate in Saccharomyces cerevisiae

Biosynthesis and Biological Activity of Carbasugars

Contact Info

Product

Resources

About