2ZCO

Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.58 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.187 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence.

Liu, C.I.Liu, G.Y.Song, Y.Yin, F.Hensler, M.E.Jeng, W.Y.Nizet, V.Wang, A.H.Oldfield, E.

(2008) Science 319: 1391-1394

  • DOI: https://doi.org/10.1126/science.1153018
  • Primary Citation of Related Structures:  
    2ZCO, 2ZCQ, 2ZCR, 2ZCS, 3W7F

  • PubMed Abstract: 

    Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of S. aureus dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration approximately 100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor-based therapy against S. aureus.


  • Organizational Affiliation

    Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dehydrosqualene synthase293Staphylococcus aureusMutation(s): 0 
Gene Names: crtM
EC: 2.5.1
UniProt
Find proteins for A9JQL9 (Staphylococcus aureus)
Explore A9JQL9 
Go to UniProtKB:  A9JQL9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA9JQL9
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.58 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.187 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.41α = 90
b = 80.41β = 90
c = 90.2γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
SOLVEphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-03-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-03-13
    Changes: Data collection, Database references