1XAL

CRYSTAL STRUCTURE OF STAPHLYOCOCCUS AUREUS 3-DEHYDROQUINATE SYNTHASE (DHQS) IN COMPLEX WITH ZN2+, NAD+ AND CARBAPHOSPHONATE (SOAK)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.203 

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This is version 1.3 of the entry. See complete history


Literature

Comparison of ligand induced conformational changes and domain closure mechanisms, between prokaryotic and eukaryotic dehydroquinate synthases.

Nichols, C.E.Ren, J.Leslie, K.Dhaliwal, B.Lockyer, M.Charles, I.Hawkins, A.R.Stammers, D.K.

(2004) J Mol Biol 343: 533-546

  • DOI: https://doi.org/10.1016/j.jmb.2004.08.039
  • Primary Citation of Related Structures:  
    1XAG, 1XAH, 1XAI, 1XAJ, 1XAL

  • PubMed Abstract: 

    Dehydroquinate synthase (DHQS) is a potential target for the development of novel broad-spectrum antimicrobial drugs, active against both prokaryotes and lower eukaryotes. Structures have been reported for Aspergillus nidulans DHQS (AnDHQS) in complexes with a range of ligands. Analysis of these AnDHQS structures showed that a large-scale domain movement occurs during the normal catalytic cycle, with a complex series of structural elements propagating substrate binding-induced conformational changes away from the active site to distal locations. Compared to corresponding fungal enzymes, DHQS from bacterial species are both mono-functional and significantly smaller. We have therefore determined the structure of Staphylococcus aureus DHQS (SaDHQS) in five liganded states, allowing comparison of ligand-induced conformational changes and mechanisms of domain closure between fungal and bacterial enzymes. This comparative analysis shows that substrate binding initiates a large-scale domain closure in both species' DHQS and that the active site stereochemistry, of the catalytically competent closed-form enzyme thus produced, is also highly conserved. However, comparison of AnDHQS and SaDHQS open-form structures, and analysis of the putative dynamic processes by which the transition to the closed-form states are made, shows a far lower degree of similarity, indicating a significant structural divergence. As a result, both the nature of the propagation of conformational change and the mechanical systems involved in this propagation are quite different between the DHQSs from the two species.


  • Organizational Affiliation

    Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-dehydroquinate synthase
A, B
354Staphylococcus aureusMutation(s): 0 
Gene Names: aroB
EC: 4.2.3.4
UniProt
Find proteins for Q6GGU4 (Staphylococcus aureus (strain MRSA252))
Explore Q6GGU4 
Go to UniProtKB:  Q6GGU4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6GGU4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.203 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.1α = 90
b = 55.1β = 90
c = 232.319γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-03-01
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations