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1w30
From Proteopedia
PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET
Overview
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.
About this Structure
1W30 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 13:05:04 2008
Categories: Mycobacterium tuberculosis | Single protein | Uracil phosphoribosyltransferase | Castro, P. | Kantardjieff, K A. | Kim, C Y. | Lekin, T. | Rho, B S. | Rupp, B. | Segelke, B W. | TBSGC, TB Structural Genomics Consortium. | Terwilliger, T. | Vasquez, C. | Warfel, N N. | Protein structure initiative | Psi | Pyrr,transferase,glycosyltransferase,psi,protein structure initiative,tb structural genomics consortium,tb | Tbsgc
