1H9Z

Human Serum Albumin Complexed With Myristic Acid and the R-(+) enantiomer of warfarin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Crystal Structure Analysis of Warfarin Binding to Human Serum Albumin: Anatomy of Drug Site I

Petitpas, I.Bhattacharya, A.A.Twine, S.East, M.Curry, S.

(2001) J Biol Chem 276: 22804

  • DOI: https://doi.org/10.1074/jbc.M100575200
  • Primary Citation of Related Structures:  
    1H9Z, 1HA2

  • PubMed Abstract: 

    Human serum albumin (HSA) is an abundant transport protein found in plasma that binds a wide variety of drugs in two primary binding sites (I and II) and can have a significant impact on their pharmacokinetics. We have determined the crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+) and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the protein with high affinity. The structures confirm that warfarin binds to drug site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular details of the protein-drug interaction. The two enantiomers of warfarin adopt very similar conformations when bound to the protein and make many of the same specific contacts with amino acid side chains at the binding site, thus accounting for the relative lack of stereospecificity of the HSA-warfarin interaction. The conformation of the warfarin binding pocket is significantly altered upon binding of fatty acids, and this can explain the observed enhancement of warfarin binding to HSA at low levels of fatty acid.


  • Organizational Affiliation

    Biophysics Section, Blackett Laboratory, Imperial College of Science, Technology, and Medicine, London SW7 2BW, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SERUM ALBUMIN585Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P02768 (Homo sapiens)
Explore P02768 
Go to UniProtKB:  P02768
PHAROS:  P02768
GTEx:  ENSG00000163631 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02768
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 187.445α = 90
b = 38.842β = 105.59
c = 95.884γ = 90
Software Package:
Software NamePurpose
CNSrefinement
MOSFLMdata reduction
SCALAdata scaling
CCP4phasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-06-20
    Type: Initial release
  • Version 1.1: 2011-11-09
    Changes: Atomic model, Data collection, Derived calculations, Non-polymer description, Other, Refinement description, Source and taxonomy, Version format compliance
  • Version 1.2: 2019-07-24
    Changes: Data collection
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description