1HA2

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

Summary for 1HA2

• Entry DOI: 10.2210/pdb1ha2/pdb
• Related: 1AO6 1BJ5 1BKE 1BM0 1E78 1E7A 1E7B 1E7C 1E7E 1E7F 1E7G 1E7H 1E7I 1H9Z 1UOR
• Descriptor: SERUM ALBUMIN, MYRISTIC ACID, S-WARFARIN, ... (4 entities in total)
• Functional Keywords: transport protein, serum protein, drug binding, anti-coagulant
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 68249.77

Authors

Petitpas, I.,Bhattacharya, A.A.,Curry, S. (deposition date: 2001-03-23, release date: 2001-06-20, Last modification date: 2024-10-23)

Primary citation

Petitpas, I.,Bhattacharya, A.A.,Twine, S.,East, M.,Curry, S.
Crystal Structure Analysis of Warfarin Binding to Human Serum Albumin: Anatomy of Drug Site I
J.Biol.Chem., 276:22804-, 2001

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.

PubMed: 11285262
DOI: 10.1074/JBC.M100575200

Experimental method

X-RAY DIFFRACTION (2.5 Å)