7DOR

E. coli GyrB ATPase domain in complex with 4-nitropheno


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.89 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Identification of new building blocks by fragment screening for discovering GyrB inhibitors.

Yu, Y.Guo, J.Cai, Z.Ju, Y.Xu, J.Gu, Q.Zhou, H.

(2021) Bioorg Chem 114: 105040-105040

  • DOI: https://doi.org/10.1016/j.bioorg.2021.105040

  • PubMed Abstract: 

    DNA gyrase is an essential DNA topoisomerase that exists only in bacteria. Since novobiocin was withdrawn from the market, new scaffolds and new mechanistic GyrB inhibitors are urgently needed. In this study, we employed fragment screening and X-ray crystallography to identify new building blocks, as well as their binding mechanisms, to support the discovery of new GyrB inhibitors. In total, 84 of the 618 chemical fragments were shown to either thermally stabilize the ATPase domain of Escherichia coli GyrB or inhibit the ATPase activity of E. coli gyrase. Among them, the IC 50 values of fragments 10 and 23 were determined to be 605.3 μM and 446.2 μM, respectively. Cocrystal structures of the GyrB ATPase domain with twelve fragment hits were successfully determined at a high resolution. All twelve fragments were deeply inserted in the pocket and formed H-bonds with Asp73 and Thr165, and six fragments formed an additional H-bond with the backbone oxygen of Val71. Fragment screening further highlighted the capability of Asp73, Thr165 and Val71 to bind chemicals and provided diverse building blocks for the design of GyrB inhibitors.


  • Organizational Affiliation

    Research Center for Drug Discovery and Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA gyrase subunit B
A, B
206Escherichia coli K-12Mutation(s): 0 
Gene Names: gyrBFAZ83_13380
EC: 5.6.2.2
UniProt
Find proteins for P0AES6 (Escherichia coli (strain K12))
Explore P0AES6 
Go to UniProtKB:  P0AES6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0AES6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.89 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.811α = 90
b = 67.519β = 90
c = 102.493γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China81773636

Revision History  (Full details and data files)

  • Version 1.0: 2021-10-27
    Type: Initial release
  • Version 1.1: 2023-11-29
    Changes: Data collection, Refinement description