4CIW

Crystal structure of Mycobacterium tuberculosis type 2 dehydroquinase in complex with (1R,4R,5R)-1,4,5-trihydroxy-3-(2-hydroxy)ethylcyclohex-2-ene-1-carboxylic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.142 
  • R-Value Observed: 0.144 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Exploring the water-binding pocket of the type II dehydroquinase enzyme in the structure-based design of inhibitors.

Blanco, B.Sedes, A.Peon, A.Otero, J.M.van Raaij, M.J.Thompson, P.Hawkins, A.R.Gonzalez-Bello, C.

(2014) J Med Chem 57: 3494-3510

  • DOI: https://doi.org/10.1021/jm500175z
  • Primary Citation of Related Structures:  
    4CIV, 4CIW, 4CIX, 4CIY

  • PubMed Abstract: 

    Structural and computational studies to explore the WAT1 binding pocket in the structure-based design of inhibitors against the type II dehydroquinase (DHQ2) enzyme are reported. The crystal structures of DHQ2 from M. tuberculosis in complex with four of the reported compounds are described. The electrostatic interaction observed between the guanidinium group of the essential arginine and the carboxylate group of one of the inhibitors in the reported crystal structures supports the recently suggested role of this arginine as the residue that triggers the release of the product from the active site. The results of the structural and molecular dynamics simulation studies revealed that the inhibitory potency is favored by promoting interactions with WAT1 and the residues located within this pocket and, more importantly, by avoiding situations where the ligands occupy the WAT1 binding pocket. The new insights can be used to advantage in the structure-based design of inhibitors.


  • Organizational Affiliation

    Centro Singular de Investigación en Química Biológica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela , 15782 Santiago de Compostela, Spain.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-DEHYDROQUINATE DEHYDRATASE146Mycobacterium tuberculosisMutation(s): 0 
EC: 4.2.1.10
UniProt
Find proteins for P9WPX7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WPX7 
Go to UniProtKB:  P9WPX7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WPX7
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.142 
  • R-Value Observed: 0.144 
  • Space Group: F 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 126.38α = 90
b = 126.38β = 90
c = 126.38γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SCALEdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-04-16
    Type: Initial release
  • Version 1.1: 2014-05-07
    Changes: Database references
  • Version 1.2: 2018-01-24
    Changes: Database references
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description