Binding of Warfarin Influences the Acid-Base Equilibrium of H242 in Sudlow Site I of Human Serum Albumin

Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the protein and serves as a binding cavity for a variety of ligands. In this study, the binding of warfarin (W) is examined using computational techniques and isothermal titration calorimetry (ITC). The structure of the docked...

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Bibliographic Details
Published in:Photochemistry and photobiology 2006-09, Vol.82 (5), p.1365-1369
Main Authors: Perry, Jennifer L., Goldsmith, Michael R., Williams, T. Richard, Radack, Kyle P., Christensen, Trine, Gorham, Justin, Pasquinelli, Melissa A., Toone, Eric J., Beratan, David N., Simon, John D.
Format: Article
Language:English
Subjects:
Acid-Base Equilibrium
Amino acids
Aqueous solutions
Binding Sites
Body fluids
Chemicals
Equilibrium
Humans
Kinetics
Models, Molecular
Protein Binding
Protein Conformation
Research s
Serum Albumin - chemistry
Serum Albumin - metabolism
Warfarin - metabolism
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Summary:Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the protein and serves as a binding cavity for a variety of ligands. In this study, the binding of warfarin (W) is examined using computational techniques and isothermal titration calorimetry (ITC). The structure of the docked warfarin anion (W−) to Site I is similar to that revealed by X-ray crystallography, with a calculated binding constant of 5.8 × 105M−1. ITC experiments (pH 7.13 and I = 0.1) carried out in three different buffers (MOPs, phosphate and Tris) reveal binding of W− is accompanied by uptake of 0.30 ± 0.02 protons from the solvent. This measurement suggests that the binding of W− is stabilized by an ion-pair interaction between protonated H242 and the phenoxide group of W−.
ISSN:0031-8655
1751-1097
DOI:10.1562/2006-02-23-RA-811