A Homologue of the Mycobacterium tuberculosis PapA5 Protein, Rif‐Orf20, Is an Acetyltransferase Involved in the Biosynthesis of Antitubercular Drug Rifamycin B by Amycolatopsis mediterranei S699

Published on May 6, 2005in ChemBioChem2.576
· DOI :10.1002/CBIC.200400387
Yeping Xiong1
Estimated H-index: 1
(OSU: Oregon State University),
Xiumei Wu8
Estimated H-index: 8
(OSU: Oregon State University),
Taifo Mahmud30
Estimated H-index: 30
(OSU: Oregon State University)
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Abstract The gene rif orf14 in the rifamycin biosynthetic gene cluster of Amycolatopsis mediterranei S699, producer of the antitubercular drug rifamycin B, encodes a protein of 272 amino acids identified as an AdoMet: 27- O -demethylrifamycin SV methyltransferase. Frameshift inactivation of rif orf14 generated a mutant of A. mediterranei S699 that produces no rifamycin B, but accumulates 27- O -demethylrifamycin SV (DMRSV) as the major new metabolite, together with a small quantity of 27- O -dem...
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Abstract Rifampicin (Rif) is one of the most potent and broad spectrum antibiotics against bacterial pathogens and is a key component of anti-tuberculosis therapy, stemming from its inhibition of the bacterial RNA polymerase (RNAP). We determined the crystal structure of Thermus aquaticus core RNAP complexed with Rif. The inhibitor binds in a pocket of the RNAP β subunit deep within the DNA/RNA channel, but more than 12 A away from the active site. The structure, combined with biochemical result...
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