2a6h

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Template:STRUCTURE 2a6h

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

Overview

Streptolydigin (Stl) is a potent inhibitor of bacterial RNA polymerases (RNAPs). The 2.4 A resolution structure of the Thermus thermophilus RNAP-Stl complex showed that, in full agreement with the available genetic data, the inhibitor binding site is located 20 A away from the RNAP active site and encompasses the bridge helix and the trigger loop, two elements that are considered to be crucial for RNAP catalytic center function. Structure-based biochemical experiments revealed additional determinants of Stl binding and demonstrated that Stl does not affect NTP substrate binding, DNA translocation, and phosphodiester bond formation. The RNAP-Stl complex structure, its comparison with the closely related substrate bound eukaryotic transcription elongation complexes, and biochemical analysis suggest an inhibitory mechanism in which Stl stabilizes catalytically inactive (preinsertion) substrate bound transcription intermediate, thereby blocking structural isomerization of RNAP to an active configuration. The results provide a basis for a design of new antibiotics utilizing the Stl-like mechanism.

About this Structure

2A6H is a Protein complex structure of sequences from Thermus thermophilus. Full crystallographic information is available from OCA.

Reference

Structural basis of transcription inhibition by antibiotic streptolydigin., Temiakov D, Zenkin N, Vassylyeva MN, Perederina A, Tahirov TH, Kashkina E, Savkina M, Zorov S, Nikiforov V, Igarashi N, Matsugaki N, Wakatsuki S, Severinov K, Vassylyev DG, Mol Cell. 2005 Sep 2;19(5):655-66. PMID:16167380 Page seeded by OCA on Sat May 3 18:40:09 2008