2F82

HMG-CoA synthase from Brassica juncea in the apo-form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for the design of potent and species-specific inhibitors of 3-hydroxy-3-methylglutaryl CoA synthases.

Pojer, F.Ferrer, J.L.Richard, S.B.Nagegowda, D.A.Chye, M.L.Bach, T.J.Noel, J.P.

(2006) Proc Natl Acad Sci U S A 103: 11491-11496

  • DOI: https://doi.org/10.1073/pnas.0604935103
  • Primary Citation of Related Structures:  
    2F82, 2F9A, 2FA0, 2FA3

  • PubMed Abstract: 

    3-Hydroxy-3-methylglutaryl CoA synthase (HMGS) catalyzes the first committed step in the mevalonate metabolic pathway for isoprenoid biosynthesis and serves as an alternative target for cholesterol-lowering and antibiotic drugs. We have determined a previously undescribed crystal structure of a eukaryotic HMGS bound covalently to a potent and specific inhibitor F-244 [(E,E)-11-[3-(hydroxymethyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4-undecadienenoic acid]. Given the accessibility of synthetic analogs of the F-244 natural product, this inhibited eukaryotic HMGS structure serves as a necessary starting point for structure-based methods that may improve the potency and species-specific selectivity of the next generation of F-244 analogs designed to target particular eukaryotic and prokaryotic HMGS.


  • Organizational Affiliation

    Howard Hughes Medical Institute, The Jack H. Skirball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HMG-CoA synthase450Brassica junceaMutation(s): 0 
UniProt
Find proteins for Q9M6U3 (Brassica juncea)
Explore Q9M6U3 
Go to UniProtKB:  Q9M6U3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9M6U3
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.197 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 61.13α = 90
b = 61.13β = 90
c = 433.67γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
NEMOdata reduction
XDSdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-07-25
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Refinement description