3IFZ

crystal structure of the first part of the Mycobacterium tuberculosis DNA gyrase reaction core: the breakage and reunion domain at 2.7 A resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.

Piton, J.Petrella, S.Delarue, M.Andre-Leroux, G.Jarlier, V.Aubry, A.Mayer, C.

(2010) PLoS One 5: e12245-e12245

  • DOI: https://doi.org/10.1371/journal.pone.0012245
  • Primary Citation of Related Structures:  
    3IFZ, 3IG0, 3M4I

  • PubMed Abstract: 

    Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.


  • Organizational Affiliation

    Unité de Dynamique Structurale des Macromolécules, Département de Biologie Structurale et Chimie, Institut Pasteur, Paris, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA gyrase subunit A
A, B
508Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: gyrAMT0006MTCY10H4.04Rv0006
EC: 5.99.1.3
UniProt
Find proteins for P9WG47 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WG47 
Go to UniProtKB:  P9WG47
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WG47
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 163.915α = 90
b = 109.66β = 120.4
c = 101.996γ = 90
Software Package:
Software NamePurpose
Adxvdata processing
AMoREphasing
BUSTER-TNTrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description