Myxopyronin inactivation of RNA polymerase

Dmitry Vassylyev group (University of Alabama) and collaborators

The groups of Dmitry Vassylyev at the University of Alabama and of Irina Artsimovich at the Ohio State University discovered the mode of RNA polymerase (RNAP) inactivation by the antibiotic myxopyronin. Desmethyl myxopyronin B (dMyx) binds deep inside the RNAP clamp head domain, which interacts with the DNA template in the transcription bubble. The antibiotic stabilizes refolding of a "switch-2", which may interfere with binding to the melted template DNA strand. Thus, myxopyronin class of antibiotics targets formation of the pre-catalytic transcription initiation complex. The work points to switch-2 as a molecular checkpoint for DNA loading in response to regulatory signals or antibiotics in multisubunit RNAPs.

Figure: Schematic drawing of the proposed mechanism of dMyx action (dwDNA = downstream DNA). [ Figure reprinted by permission from Macmillan Publishers Ltd: Nature, 2009]

Citation:
Belogurov, GA, Vassylyeva, MN, Sevostyanova, A, Appleman, JR, Xiang, AX, Lira, R, Webber, SE, Klyuyev, S, Nudler, E, Artsimovitch, I, Vassylyev, DG. Transcription inactivation through local refolding of the RNA polymerase structure, Nature 457, 332-335 (2009). DOI: 10.1038/nature07510