1w30

PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET

spinqualitylabelsall models 1w30, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1w30 is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Activity: Uracil phosphoribosyltransferase, with EC number 2.4.2.9 Resources: FirstGlance, OCA, RCSB, PDBsum Function [PYRR_MYCTU] Regulates the transcription of the pyrimidine nucleotide (pyr) operon in response to exogenous pyrimidines (By similarity). Also displays a weak uracil phosphoribosyltransferase activity which is not physiologically significant (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The Mycobacterium tuberculosis pyrR gene (Rv1379) encodes a protein that regulates the expression of pyrimidine-nucleotide biosynthesis (pyr) genes in a UMP-dependent manner. Because pyrimidine biosynthesis is an essential step in the progression of TB, the gene product pyrR is an attractive antitubercular drug target. The 1.9 A native structure of Mtb pyrR determined by the TB Structural Genomics Consortium facilities in trigonal space group P3(1)21 is reported, with unit-cell parameters a = 66.64, c = 154.72 A at 120 K and two molecules in the asymmetric unit. The three-dimensional structure and residual uracil phosphoribosyltransferase activity point to a common PRTase ancestor for pyrR. However, while PRPP- and UMP-binding sites have been retained in Mtb pyrR, a distinct dimer interaction among subunits creates a deep positively charged cleft capable of binding pyr mRNA. In silico screening of pyrimidine-nucleoside analogs has revealed a number of potential lead compounds that, if bound to Mtb pyrR, could facilitate transcriptional attenuation, particularly cyclopentenyl nucleosides. Structure of pyrR (Rv1379) from Mycobacterium tuberculosis: a persistence gene and protein drug target.,Kantardjieff KA, Vasquez C, Castro P, Warfel NM, Rho BS, Lekin T, Kim CY, Segelke BW, Terwilliger TC, Rupp B Acta Crystallogr D Biol Crystallogr. 2005 Apr;61(Pt 4):355-64. Epub 2005, Mar 24. PMID:15805589 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase

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