2QNX

Crystal structure of the complex between the mycobacterium beta-ketoacyl-acyl carrier protein synthase III (FABH) and 11-[(decyloxycarbonyl)dithio]-undecanoic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.213 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Separate Entrance and Exit Portals for Ligand Traffic in Mycobacterium tuberculosis FabH

Sachdeva, S.Musayev, F.N.Alhamadsheh, M.M.Scarsdale, J.N.Wright, H.T.Reynolds, K.A.

(2008) Chem Biol 15: 402-412

  • DOI: https://doi.org/10.1016/j.chembiol.2008.03.007
  • Primary Citation of Related Structures:  
    2QNX, 2QNY, 2QNZ, 2QO0, 2QO1

  • PubMed Abstract: 

    Mycobacterium tuberculosis FabH initiates type II fatty acid synthase-catalyzed formation of the long chain (C(16)-C(22)) acyl-coenzyme A (CoA) precursors of mycolic acids, which are major constituents of the bacterial cell envelope. Crystal structures of M. tuberculosis FabH (mtFabH) show the substrate binding site to be a buried, extended L-shaped channel with only a single solvent access portal. Entrance of an acyl-CoA substrate through the solvent portal would require energetically unfavorable reptational threading of the substrate to its reactive position. Using a class of FabH inhibitors, we have tested an alternative hypothesis that FabH exists in an "open" form during substrate binding and product release, and a "closed" form in which catalysis and intermediate steps occur. This hypothesis is supported by mass spectrometric analysis of the product profile and crystal structures of complexes of mtFabH with these inhibitors.


  • Organizational Affiliation

    Department of Chemistry, Portland State University, Portland, OR 97207, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-oxoacyl-[acyl-carrier-protein] synthase 3
A, B
335Mycobacterium tuberculosisMutation(s): 0 
Gene Names: fabH
EC: 2.3.1.41
UniProt
Find proteins for P9WNG3 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WNG3 
Go to UniProtKB:  P9WNG3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WNG3
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
UDT PDBBind:  2QNX IC50: 2400 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.213 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.285α = 90
b = 88.981β = 90
c = 230.252γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CNSrefinement
AMoREphasing
CrystalCleardata collection
d*TREKdata reduction
d*TREKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-05-06
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2019-07-24
    Changes: Data collection, Derived calculations, Refinement description
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description