3VJD

Crystal structure of the Y248A mutant of C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.164 

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This is version 1.2 of the entry. See complete history


Literature

Binding modes of zaragozic acid A to human squalene synthase and staphylococcal dehydrosqualene synthase

Liu, C.I.Jeng, W.Y.Chang, W.J.Ko, T.P.Wang, A.H.J.

(2012) J Biol Chem 287: 18750-18757

  • DOI: https://doi.org/10.1074/jbc.M112.351254
  • Primary Citation of Related Structures:  
    3VJ8, 3VJ9, 3VJA, 3VJB, 3VJC, 3VJD, 3VJE

  • PubMed Abstract: 

    Zaragozic acids (ZAs) belong to a family of fungal metabolites with nanomolar inhibitory activity toward squalene synthase (SQS). The enzyme catalyzes the committed step of sterol synthesis and has attracted attention as a potential target for antilipogenic and antiinfective therapies. Here, we have determined the structure of ZA-A complexed with human SQS. ZA-A binding induces a local conformational change in the substrate binding site, and its C-6 acyl group also extends over to the cofactor binding cavity. In addition, ZA-A effectively inhibits a homologous bacterial enzyme, dehydrosqualene synthase (CrtM), which synthesizes the precursor of staphyloxanthin in Staphylococcus aureus to cope with oxidative stress. Size reduction at Tyr(248) in CrtM further increases the ZA-A binding affinity, and it reveals a similar overall inhibitor binding mode to that of human SQS/ZA-A except for the C-6 acyl group. These structures pave the way for further improving selectivity and development of a new generation of anticholesterolemic and antimicrobial inhibitors.


  • Organizational Affiliation

    Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dehydrosqualene synthase293Staphylococcus aureusMutation(s): 1 
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
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TLA
Query on TLA

Download Ideal Coordinates CCD File 
B [auth A]L(+)-TARTARIC ACID
C4 H6 O6
FEWJPZIEWOKRBE-JCYAYHJZSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.164 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.587α = 90
b = 79.587β = 90
c = 90.757γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-11
    Type: Initial release
  • Version 1.1: 2013-07-24
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description