2a68

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spinqualitylabelsall models 2a68, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic rifabutin

Overview

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.

About this Structure

2A68 is a Protein complex structure of sequences from Thermus thermophilus with RBT, ZN and MG as ligands. Active as DNA-directed RNA polymerase, with EC number 2.7.7.6 Full crystallographic information is available from OCA.

Reference

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

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