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Molecular insights into the mechanism of phenotypic tolerance to rifampicin conferred on mycobacterial RNA polymerase by MsRbpA

Dey, Abhinav and Verma, Amit Kumar and Chatterji, Dipankar (2011) Molecular insights into the mechanism of phenotypic tolerance to rifampicin conferred on mycobacterial RNA polymerase by MsRbpA. In: Microbiology, 157 (Part 7). pp. 2056-2071.

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Official URL: http://mic.sgmjournals.org/content/157/7/2056.full

Abstract

The protein MsRbpA from Mycobacterium smegmatis rescues RNA polymerase (RNAP) from the inhibitory effect of rifampicin (Rif). We have reported previously that MsRbpA interacts with the beta-subunit of RNAP and that the effect of MsRbpA on Rif-resistant (Rif(R)) RNAP is minimal. Here we attempted to gain molecular insights into the mechanism of action of this protein with respect to its role in rescuing RNAP from Rif-mediated transcription inhibition. Our experimental approach comprised multiple-round transcription assays, fluorescence spectroscopy, MS and surface plasmon resonance in order to meet the above objective. Based on our molecular studies we propose here that Rif is released from its binding site in the RNAP-Rif complex in the presence of MsRbpA. Biophysical studies reveal that the location of MsRbpA on RNAP is at the junction of the beta- and beta'-subunits, close to the Rif-binding site and the (i + 1) site on RNAP.

Item Type: Journal Article
Publication: Microbiology
Publisher: Society for General Microbiology
Additional Information: Copyright of this article belongs to Society for General Microbiology.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 30 Aug 2011 06:43
Last Modified: 30 Aug 2011 06:43
URI: http://eprints.iisc.ac.in/id/eprint/39960

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