1W93

Crystal Structure of Biotin Carboxylase Domain of Acetyl-Coenzyme A Carboxylase from Saccharomyces cerevisiae


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.323 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.254 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A Mechanism for the Potent Inhibition of Eukaryotic Acetyl-Coenzyme a Carboxylase by Soraphen A, a Macrocyclic Polyketide Natural Product

Shen, Y.Volrath, S.L.Weatherly, S.C.Elich, T.D.Tong, L.

(2004) Mol Cell 16: 881

  • DOI: https://doi.org/10.1016/j.molcel.2004.11.034
  • Primary Citation of Related Structures:  
    1W93, 1W96

  • PubMed Abstract: 

    Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism. Soraphen A, a macrocyclic polyketide natural product, is a nanomolar inhibitor against the biotin carboxylase (BC) domain of human, yeast, and other eukaryotic ACCs. Here we report the crystal structures of the yeast BC domain, alone and in complex with soraphen A. Soraphen has extensive interactions with an allosteric site, about 25 A from the active site. The specificity of soraphen is explained by large structural differences between the eukaryotic and prokaryotic BC in its binding site, confirmed by our studies on the effects of single-site mutations in this binding site. Unexpectedly, our structures suggest that soraphen may bind in the BC dimer interface and inhibit the BC activity by disrupting the oligomerization of this domain. Observations from native gel electrophoresis confirm this structural insight. The structural information provides a foundation for structure-based design of new inhibitors against these enzymes.


  • Organizational Affiliation

    Department of Biological Sciences, Columbia University, New York, NY 10027, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ACETYL-COENZYME A CARBOXYLASE553Saccharomyces cerevisiaeMutation(s): 0 
EC: 6.4.1.2
UniProt
Find proteins for Q00955 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore Q00955 
Go to UniProtKB:  Q00955
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ00955
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.323 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.254 
  • Space Group: P 62
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.74α = 90
b = 101.74β = 90
c = 145.83γ = 120
Software Package:
Software NamePurpose
CNSrefinement
HKLdata reduction
HKLdata scaling
COMOphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-01-04
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance