6C04

Mtb RNAP Holo/RbpA/double fork DNA -closed clamp

Summary for 6C04

• Entry DOI: 10.2210/pdb6c04/pdb
• EMDB information: 7320
• Descriptor: DNA-directed RNA polymerase subunit alpha, MAGNESIUM ION, DNA-directed RNA polymerase subunit beta, ... (10 entities in total)
• Functional Keywords: initiation, transcription bubble, closed clamp, transcription, transcription-dna complex, transcription/dna
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 11
• Total formula weight: 471849.66

Authors

Darst, S.A.,Campbell, E.A.,Boyaci Selcuk, H.,Chen, J.,Lilic, M. (deposition date: 2017-12-27, release date: 2018-03-28, Last modification date: 2024-03-13)

Primary citation

Boyaci, H.,Chen, J.,Lilic, M.,Palka, M.,Mooney, R.A.,Landick, R.,Darst, S.A.,Campbell, E.A.
Fidaxomicin jamsMycobacterium tuberculosisRNA polymerase motions needed for initiation via RbpA contacts.
Elife, 7:-, 2018

PubMed Abstract: Fidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective against RNAP in vitro, but clinical use of Fdx is limited to treating intestinal infections due to poor absorption. To identify the structural determinants of Fdx binding to RNAP, we determined the 3.4 Å cryo-electron microscopy structure of a complete RNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin, explaining its strong effect on . Additional structures define conformational states of RNAP between the free apo-holoenzyme and the promoter-engaged open complex ready for transcription. The results establish that Fdx acts like a doorstop to jam the enzyme in an open state, preventing the motions necessary to secure promoter DNA in the active site. Our results provide a structural platform to guide development of anti-tuberculosis antimicrobials based on the Fdx binding pocket.

PubMed: 29480804
DOI: 10.7554/eLife.34823

Experimental method

ELECTRON MICROSCOPY (3.27 Å)