6C06
Mycobacterium tuberculosis RNAP Holo/RbpA/Fidaxomicin
Summary for 6C06
| Entry DOI | 10.2210/pdb6c06/pdb |
| Related | 6BZO 6C04 6C05 |
| EMDB information | 7323 |
| Descriptor | DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (9 entities in total) |
| Functional Keywords | initiation, antibiotic, switch region inhibitor, transcription, transcription-antibiotic complex, transcription/antibiotic |
| Biological source | Mycobacterium tuberculosis More |
| Cellular location | Cytoplasm : A0A045HD00 |
| Total number of polymer chains | 7 |
| Total formula weight | 437917.00 |
| 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 Cited by 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: 29480804DOI: 10.7554/eLife.34823 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (5.15 Å) |
Structure validation
Download full validation report
