Binding of warfarin influences the acid-base equilibrium of H242 in sudlow site I of human serum albumin.

Journal Article

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 x 10(5) M(-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-.

Full Text

Duke Authors

Cited Authors

  • Perry, JL; Goldsmith, MR; Williams, TR; Radack, KP; Christensen, T; Gorham, J; Pasquinelli, MA; Toone, EJ; Beratan, DN; Simon, JD

Published Date

  • September 2006

Published In

Volume / Issue

  • 82 / 5

Start / End Page

  • 1365 - 1369

PubMed ID

  • 16563025

International Standard Serial Number (ISSN)

  • 0031-8655

Digital Object Identifier (DOI)

  • 10.1562/2006-02-23-RA-811

Language

  • eng

Conference Location

  • United States