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'''PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET''' | '''PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET''' | ||
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[[Category: Vasquez, C.]] | [[Category: Vasquez, C.]] | ||
[[Category: Warfel, N N.]] | [[Category: Warfel, N N.]] | ||
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[[Category: | [[Category: Psi]] | ||
[[Category: | [[Category: Pyrr,transferase,glycosyltransferase,psi,protein structure initiative,tb structural genomics consortium,tb]] | ||
[[Category: | [[Category: Tbsgc]] | ||
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Revision as of 10:05, 3 May 2008
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
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- 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
