6C05

Mycobacterium tuberculosis RNAP Holo/RbpA in relaxed state


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 5.15 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Fidaxomicin jamsMycobacterium tuberculosisRNA polymerase motions needed for initiation via RbpA contacts.

Boyaci, H.Chen, J.Lilic, M.Palka, M.Mooney, R.A.Landick, R.Darst, S.A.Campbell, E.A.

(2018) Elife 7

  • DOI: https://doi.org/10.7554/eLife.34823
  • Primary Citation of Related Structures:  
    6BZO, 6C04, 6C05, 6C06

  • PubMed Abstract: 

    Fidaxomicin (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 Å 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.


  • Organizational Affiliation

    The Rockefeller University, New York, United States.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit alpha
A, B
347Mycobacterium tuberculosisMutation(s): 0 
Gene Names: 
EC: 2.7.7.6
UniProt
Find proteins for P9WGZ1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WGZ1
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit beta1,181Mycobacterium tuberculosisMutation(s): 0 
Gene Names: rpoBSAMEA2682864_01701
EC: 2.7.7.6
UniProt
Find proteins for P9WGY9 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WGY9
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit beta'1,324Mycobacterium tuberculosisMutation(s): 0 
Gene Names: rpoCrpoC_1CLD25_03785ERS007665_00591ERS023446_00410ERS031537_00289ERS124361_01694SAMEA2682864_01702
EC: 2.7.7.6
UniProt
Find proteins for P9WGY7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WGY7
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit omega110Mycobacterium tuberculosisMutation(s): 0 
Gene Names: rpoZERS007672_03979ERS007703_04032ERS007720_04749ERS027652_00548ERS027654_02543ERS027656_03959ERS124361_02246
EC: 2.7.7.6
UniProt
Find proteins for P9WGY5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
RNA polymerase sigma factor SigA531Mycobacterium tuberculosisMutation(s): 0 
Gene Names: 
UniProt
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
RNA polymerase-binding protein RbpAG [auth J]111Mycobacterium tuberculosisMutation(s): 0 
Gene Names: 
UniProt
Find proteins for P9WHJ5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WHJ5
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Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 5.15 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-03-28
    Type: Initial release
  • Version 1.1: 2019-12-18
    Changes: Other