6c04
From Proteopedia
Mtb RNAP Holo/RbpA/double fork DNA -closed clamp
Structural highlights
Function[A0A045IP01_MYCTX] Binds to RNA polymerase (RNAP), stimulating transcription from principal, but not alternative sigma factor promoters.[HAMAP-Rule:MF_01483] [A0A045J9E2_MYCTX] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU004279][SAAS:SAAS00365746] [V9Z879_MYCTX] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU363031] [A0A045J8T1_MYCTX] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059] [A0A0T9N9K3_MYCTX] Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.[HAMAP-Rule:MF_00366][SAAS:SAAS00298387] [A0A045HD00_MYCTX] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth.[SAAS:SAAS00535554] Publication Abstract from PubMedFidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective against Mycobacterium tuberculosis RNAP in vitro, but clinical use of Fdx is limited to treating Clostridium difficile intestinal infections due to poor absorption. To identify the structural determinants of Fdx binding to RNAP, we determined the 3.4 A cryo-electron microscopy structure of a complete M. tuberculosis RNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin, explaining its strong effect on M. tuberculosis. Additional structures define conformational states of M. tuberculosis 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. Fidaxomicin jams Mycobacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts.,Boyaci H, Chen J, Lilic M, Palka M, Mooney RA, Landick R, Darst SA, Campbell EA Elife. 2018 Feb 26;7. pii: 34823. doi: 10.7554/eLife.34823. PMID:29480804[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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