RCSB PDB - 1DQ9: COMPLEX OF CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG-COA

 1DQ9

COMPLEX OF CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG-COA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted HMGClick on this verticalbar to view details

This is version 1.4 of the entry. See complete history


Literature

Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis.

Istvan, E.S.Palnitkar, M.Buchanan, S.K.Deisenhofer, J.

(2000) EMBO J 19: 819-830

  • DOI: https://doi.org/10.1093/emboj/19.5.819
  • Primary Citation of Related Structures:  
    1DQ8, 1DQ9, 1DQA

  • PubMed Abstract: 

    3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyzes the formation of mevalonate, the committed step in the biosynthesis of sterols and isoprenoids. The activity of HMGR is controlled through synthesis, degradation and phosphorylation to maintain the concentration of mevalonate-derived products. In addition to the physiological regulation of HMGR, the human enzyme has been targeted successfully by drugs in the clinical treatment of high serum cholesterol levels. Three crystal structures of the catalytic portion of human HMGR in complexes with HMG-CoA, with HMG and CoA, and with HMG, CoA and NADP(+), provide a detailed view of the enzyme active site. Catalytic portions of human HMGR form tight tetramers. The crystal structure explains the influence of the enzyme's oligomeric state on the activity and suggests a mechanism for cholesterol sensing. The active site architecture of human HMGR is different from that of bacterial HMGR; this may explain why binding of HMGR inhibitors to bacterial HMGRs has not been reported.


  • Organizational Affiliation

    Howard Hughes Medical Institute, Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, TX 75235-9050, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (HMG-COA REDUCTASE)
A, B, C, D
467Homo sapiensMutation(s): 1 
EC: 1.1.1.34
UniProt & NIH Common Fund Data Resources
Find proteins for P04035 (Homo sapiens)
Explore P04035 
Go to UniProtKB:  P04035
PHAROS:  P04035
GTEx:  ENSG00000113161 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04035
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.207 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.58α = 90
b = 171.2β = 116.59
c = 80.37γ = 90
Software Package:
Software NamePurpose
AMoREphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted HMGClick on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-03-08
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-03-14
    Changes: Database references
  • Version 1.4: 2024-02-07
    Changes: Data collection, Database references, Derived calculations