Disease relevance of pyrE

• RNA polymerase involvement in the regulation of expression of Salmonella typhimurium pyr genes. Isolation and characterization of a fluorouracil-resistant mutant with high, constitutive expression of the pyrB and pyrE genes due to a mutation in rpoBC [1].

High impact information on pyrE

• The specific activities of aspartate transcarbamylase and orotate phosphoribosyltransferase are 40-fold and 7-fold higher in the mutant than in the parent strain when grown in minimal media [1].
• Orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10) catalyzes the formation of the nucleotide orotidine-5'-monophosphate from orotate and 5-phosphoribosyl-1-pyrophosphate (PRPP) [2].
• Active site lysines in orotate phosphoribosyltransferase [2].
• In de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotic acid and alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP) [3].
• Salmonella typhimurium orotate phosphoribosyltransferase (OPRTase) catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP) [4].

Chemical compound and disease context of pyrE

• The 2.6-A structure of the Salmonella typhimurium orotate phosphoribosyltransferase (OPRTase) complexed with its product orotidine monophosphate (OMP) provides the first detailed image of a member of this group of enzymes [5].
• Locations and functional roles of conserved lysine residues in Salmonella typhimurium orotate phosphoribosyltransferase [4].

Biological context of pyrE

• Together with the phenotype of the rpoBC mutant, these results indicate that expression of pyrB and pyrE is regulated by the mRNA chain growth rate, which is controlled by the cellular UTP pool [6].
• We investigated the transcription kinetics of RNA polymerase from an rpoBC mutant of Salmonella typhimurium which showed highly elevated, constitutive expression of the pyrB and pyrE genes as well as an increased cellular pool of UTP [6].
• The leader region does not show any features resembling the attenuators found preceding the pyrBI operon and the pyrE gene [7].
• The mutation was found to be a single base-pair transition of GC to AT, and occurred within a region of dyad symmetry (attenuator) located just upstream of the pyrE structural gene [8].

Associations of pyrE with chemical compounds

• Moreover, aspartate transcarbamylase (encoded by pyrB) became further derepressed upon cytidine addition, whereas no change occurred in the levels of the last two enzymes (encoded by pyrE and pyrF) of the pyrimidine pathway [9].
• (i) The expression of pyrB, pyrE, and pyrF is controlled by a uridine nucleotide in a noncoordinate manner [10].
• However, the affected genes of several such 'FOR' (FO-resistant) mutants were shown by transduction of map in the short cysE-pyrE segment, which includes nearly all known rfa genes responsible for synthesis of LPS core [11].
• Orotate phosphoribosyltransferase (OMP synthase, EC 2.4.2.10) forms the UMP precursor orotidine 5'-monophophate (OMP) from orotate and alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP) [12].
• There are five highly conserved lysine residues (Lys-19, -26, -73, -100, and -103) in S. typhimurium OPRTase [4].

Other interactions of pyrE

• Mutations in spoT map between gltC and pyrE at 79 min [13].
• Two mutants with the InsTet(G-)1 insertion in the gene pyrE or argA survived this procedure, indicating a reduced intracellular growth rate in J774-A.1 cells [14].
• They did not change the linkage of more distant markers pyrE and cysE [15].
• However, the product of the PRibPP synthetase reaction, can be detected quantitatively even in crude protein extracts through the addition of two enzymes (orotate phosphoribosyltransferase and inorganic pyrophosphatase) that catalyze the conversion of PRibPP into a spectroscopically detectable nucleotide product (orotidylate) [16].
• Dihydroorotate dehydrogenase, orotate phosphoribosyltransferase and orotidine-5'-monophosphate (OMP) decarboxylase showed peaks of activity corresponding to the mid-point of the exponential phase of growth while remaining comparatively stable in the stationary phase [17].

References