5J1Y

Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with 1-(pyrrolidin-1-yl)-3-(tetrahydrofuran-3-yl)propan-1-one at 1.81A resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 

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Ligand Structure Quality Assessment 


This is version 2.3 of the entry. See complete history


Literature

Fragment-Sized EthR Inhibitors Exhibit Exceptionally Strong Ethionamide Boosting Effect in Whole-Cell Mycobacterium tuberculosis Assays.

Nikiforov, P.O.Blaszczyk, M.Surade, S.Boshoff, H.I.Sajid, A.Delorme, V.Deboosere, N.Brodin, P.Baulard, A.R.Barry, C.E.Blundell, T.L.Abell, C.

(2017) ACS Chem Biol 12: 1390-1396

  • DOI: https://doi.org/10.1021/acschembio.7b00091
  • Primary Citation of Related Structures:  
    5IOY, 5IOZ, 5IP6, 5IPA, 5J1R, 5J1U, 5J1Y, 5J3L

  • PubMed Abstract: 

    Small-molecule inhibitors of the mycobacterial transcriptional repressor EthR have previously been shown to act as boosters of the second-line antituberculosis drug ethionamide. Fragment-based drug discovery approaches have been used in the past to make highly potent EthR inhibitors with ethionamide boosting activity both in vitro and ex vivo. Herein, we report the development of fragment-sized EthR ligands with nanomolar minimum effective concentration values for boosting the ethionamide activity in Mycobacterium tuberculosis whole-cell assays.


  • Organizational Affiliation

    Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
EthR216Mycobacterium tuberculosisMutation(s): 0 
Gene Names: 
UniProt
Find proteins for P9WMC1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WMC1 
Go to UniProtKB:  P9WMC1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WMC1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P87
Query on P87

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
3-[(3S)-oxolan-3-yl]-1-(pyrrolidin-1-yl)propan-1-one
C11 H19 N O2
QMNDAUGCAGNHLO-JTQLQIEISA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 121.293α = 90
b = 121.293β = 90
c = 33.682γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
xia2data reduction
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Engineering and Physical Sciences Research CouncilUnited Kingdom--
Bill & Melinda Gates FoundationUnited States--
European Union--

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-05
    Type: Initial release
  • Version 2.0: 2017-07-12
    Changes: Atomic model, Derived calculations
  • Version 2.1: 2017-09-13
    Changes: Author supporting evidence
  • Version 2.2: 2017-12-06
    Changes: Database references
  • Version 2.3: 2024-01-10
    Changes: Data collection, Database references, Refinement description