2a69

Crystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with antibiotic rifapentin

spinqualitylabelsall models 2a69, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2a69 is a 12 chain structure with sequence from Thermus thermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, RPT, ZN Related: 1iw7, 1smy, 2a68, 1a6e, 1a6h Activity: DNA-directed RNA polymerase, with EC number 2.7.7.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, TOPSAN Function [RPOA_THETH] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [RPOC_THET8] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. [RPOB_THET8] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. 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 Rifamycins, the clinically important antibiotics, target bacterial RNA polymerase (RNAP). A proposed mechanism in which rifamycins sterically block the extension of nascent RNA beyond three nucleotides does not alone explain why certain RNAP mutations confer resistance to some but not other rifamycins. Here we show that unlike rifampicin and rifapentin, and contradictory to the steric model, rifabutin inhibits formation of the first and second phosphodiester bonds. We report 2.5 A resolution structures of rifabutin and rifapentin complexed with the Thermus thermophilus RNAP holoenzyme. The structures reveal functionally important distinct interactions of antibiotics with the initiation sigma factor. Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo-holoenzyme, whereas an increase in Mg2+ concentration confers resistance to rifamycins. We propose that a rifamycin-induced signal is transmitted over approximately 19 A to the RNAP active site to slow down catalysis. Based on structural predictions, we designed enzyme substitutions that apparently interrupt this allosteric signal. Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins.,Artsimovitch I, Vassylyeva MN, Svetlov D, Svetlov V, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Tahirov TH, Vassylyev DG Cell. 2005 Aug 12;122(3):351-63. PMID:16096056 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase Sigma factor Temp1

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