1DFH

X-RAY STRUCTURE OF ESCHERICHIA COLI ENOYL REDUCTASE WITH BOUND NAD AND THIENO-DIAZABORINE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Work: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

A mechanism of drug action revealed by structural studies of enoyl reductase.

Baldock, C.Rafferty, J.B.Sedelnikova, S.E.Baker, P.J.Stuitje, A.R.Slabas, A.R.Hawkes, T.R.Rice, D.W.

(1996) Science 274: 2107-2110

  • DOI: https://doi.org/10.1126/science.274.5295.2107
  • Primary Citation of Related Structures:  
    1DFG, 1DFH, 1DFI

  • PubMed Abstract: 

    Enoyl reductase (ENR), an enzyme involved in fatty acid biosynthesis, is the target for antibacterial diazaborines and the front-line antituberculosis drug isoniazid. Analysis of the structures of complexes of Escherichia coli ENR with nicotinamide adenine dinucleotide and either thienodiazaborine or benzodiazaborine revealed the formation of a covalent bond between the 2' hydroxyl of the nicotinamide ribose and a boron atom in the drugs to generate a tight, noncovalently bound bisubstrate analog. This analysis has implications for the structure-based design of inhibitors of ENR, and similarities to other oxidoreductases suggest that mimicking this molecular linkage may have generic applications in other areas of medicinal chemistry.


  • Organizational Affiliation

    Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK. D.Rice@sheffield.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ENOYL ACYL CARRIER PROTEIN REDUCTASE
A, B
261Escherichia coliMutation(s): 0 
EC: 1.3.1.9
UniProt
Find proteins for P0AEK4 (Escherichia coli (strain K12))
Explore P0AEK4 
Go to UniProtKB:  P0AEK4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0AEK4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAD
Query on NAD

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
NICOTINAMIDE-ADENINE-DINUCLEOTIDE
C21 H27 N7 O14 P2
BAWFJGJZGIEFAR-NNYOXOHSSA-N
TDB
Query on TDB

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B]
6-METHYL-2(PROPANE-1-SULFONYL)-2H-THIENO[3,2-D][1,2,3]DIAZABORININ-1-OL
C9 H13 B N2 O3 S2
TVXLILKNSPCVRB-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Work: 0.194 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.9α = 90
b = 80.9β = 90
c = 328.3γ = 120
Software Package:
Software NamePurpose
CCP4model building
TNTrefinement
MOSFLMdata reduction
Agrovatadata scaling
CCP4phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-01-28
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description, Structure summary