1W30

PyrR of Mycobacterium Tuberculosis as a potential drug target

Summary for 1W30

• Entry DOI: 10.2210/pdb1w30/pdb
• Descriptor: PYRR BIFUNCTIONAL PROTEIN (2 entities in total)
• Functional Keywords: pyrr, transferase, glycosyltransferase, psi, protein structure initiative, tb structural genomics consortium, tb, tbsgc
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 2
• Total formula weight: 43259.19

Authors

Kantardjieff, K.A.,Vasquez, C.,Castro, P.,Warfel, N.N.,Rho, B.-S.,Lekin, T.,Kim, C.-Y.,Segelke, B.W.,Terwilliger, T.,Rupp, B.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2004-07-11, release date: 2004-09-29, Last modification date: 2023-12-13)

Primary citation

Kantardjieff, K.A.,Vasquez, C.,Castro, P.,Warfel, N.N.,Rho, B.-S.,Lekin, T.,Kim, C.-Y.,Segelke, B.W.,Terwilliger, T.,Rupp, B.
Structure of Pyrr (Rv1379) from Mycobacterium Tuberculosis: A Persistence Gene and Protein Drug Target
Acta Crystallogr.,Sect.D, 61:355-, 2005

PubMed Abstract: 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.

PubMed: 15805589
DOI: 10.1107/S090744490403389X

Experimental method

X-RAY DIFFRACTION (1.9 Å)