2NV6

Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.201 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history. 


Literature

Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid.

Vilcheze, C., Wang, F., Arai, M., Hazbon, M.H., Colangeli, R., Kremer, L., Weisbrod, T.R., Alland, D., Sacchettini, J.C., Jacobs Jr., W.R.

(2006) Nat Med 12: 1027-1029

  • DOI: https://doi.org/10.1038/nm1466
  • Primary Citation of Related Structures:  
    2NV6

  • PubMed Abstract: 

    Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis.

    • Organizational Affiliation: 

    Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Enoyl-[acyl-carrier-protein] reductase [NADH268Mycobacterium tuberculosisMutation(s): 2 
Gene Names: inhA
EC: 1.3.1.9
UniProt
Find proteins for P9WGR1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WGR1 
Go to UniProtKB:  P9WGR1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WGR1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZID
Query on ZID
Download Ideal Coordinates CCD File 
B [auth A]ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE DINUCLEOTIDE
C27 H30 N8 O15 P2
SURAWYIAXPVHGO-XDBKRARRSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ZID Binding MOAD:  2NV6 IC50: 323 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.201 
  • Space Group: P 62 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.278α = 90
b = 98.278β = 90
c = 139.243γ = 120
Software Package:
Software NamePurpose
CNSrefinement
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-11-21
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-30
    Changes: Data collection, Refinement description