PMID: 11933059Apr 5, 2002Paper

Probing the structure of the warfarin-binding site on human serum albumin using site-directed mutagenesis

Proteins
C E PetersenN V Bhagavan

Abstract

The binding of warfarin to the following human serum albumin (HSA) mutants was examined: K195M, K199M, F211V, W214L, R218M, R222M, H242V, and R257M. Warfarin bound to human serum albumin (HSA) exhibits an intrinsic fluorescence that is approximately 10-fold greater than the corresponding signal for warfarin in aqueous solution. This property of the warfarin/HSA complex has been widely used to determine the dissociation constant for the interaction. In the present study, such a technique was used to show that specific substitutions in subdomain 2A altered the affinity of HSA for warfarin. The fluorescence of warfarin/mutant HSA complexes varied widely from the fluorescence of the warfarin/wild-type HSA complex at pH = 7.4, suggesting changes in the structure of the complex resulting from specific substitutions. The fluorescence of the warfarin/wild-type HSA complex increases about twofold as the pH is increased from 6.0 to 9.0 due to the neutral-to-base (N-B) transition, a conformational change that occurs in HSA as a function of pH. Changes in the fluorescence of warfarin/mutant HSA complexes as a function of pH suggests novel behavior for most HSA species examined. For the HSA mutants F211V and H242V, the midpoint of the N-B t...Continue Reading

References

May 1, 1976·Clinical Pharmacology and Therapeutics·A YacobiG Levy
Jul 16, 1992·Nature·X M He, D C Carter
Jul 30, 1992·Nature·J V Malheiros
Sep 26, 1986·Biochimica Et Biophysica Acta·J F Labro, L H Janssen
Nov 26, 1973·Annals of the New York Academy of Sciences·C F Chignell
Dec 20, 1982·Biochimica Et Biophysica Acta·S Wanwimolruk, D J Birkett
Jan 15, 1983·Biochemical Pharmacology·W F van der Giesen, J Wilting
Dec 1, 1981·Clinical Pharmacology and Therapeutics·R J PiroliE S Vesell
Sep 25, 1995·Biochemical and Biophysical Research Communications·C E PetersenN V Bhagavan
Jan 1, 1994·Advances in Protein Chemistry·D C Carter, J X Ho
Nov 26, 1999·Biochimica Et Biophysica Acta·S CurryN P Franks
Feb 1, 2000·The Journal of Biological Chemistry·M DockalF Rüker
Mar 23, 2000·Chemico-biological Interactions·C E PetersenN V Bhagavan
Apr 8, 2000·Journal of Biomedical Science·C E HaN V Bhagavan
Sep 7, 2000·Protein Science : a Publication of the Protein Society·M DockalF Rüker
Apr 4, 2001·The Journal of Biological Chemistry·I PetitpasS Curry

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Citations

Feb 24, 2009·European Journal of Drug Metabolism and Pharmacokinetics·Christine Tesseromatis, Anastasia Alevizou
Aug 27, 2013·The Protein Journal·Mohammed J FarooqiLorenzo Brancaleon
Jun 13, 2009·The Journal of Biological Chemistry·Claudia A BlindauerPeter J Sadler
Jul 6, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·He-Dong BianHong Liang
Oct 29, 2014·Genome Biology and Evolution·Alessandra MozziManuela Sironi
Mar 28, 2006·Photochemistry and Photobiology·Jennifer L PerryJohn D Simon
Oct 30, 2010·Journal of Molecular Recognition : JMR·Ian A NichollsHenning Henschel
Dec 1, 2009·IUBMB Life·Paolo Ascenzi, Mauro Fasano
Apr 23, 2013·Biochimica Et Biophysica Acta·Chung-Eun Ha, Nadhipuram V Bhagavan
Sep 12, 2009·Drug Metabolism and Pharmacokinetics·Stephen Curry
Sep 12, 2009·Drug Metabolism and Pharmacokinetics·Victor Tuan Giam ChuangMasaki Otagiri
Jul 8, 2008·Journal of Molecular Biology·Patricia A ZunszainStephen Curry
Aug 3, 2016·Physical Chemistry Chemical Physics : PCCP·B A RussellY Chen
Oct 30, 2016·International Journal of Biological Macromolecules·Mohammed J FarooqiLorenzo Brancaleon
Oct 11, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ken-ichi KanekoMasaki Otagiri
Aug 19, 2007·The Journal of Physical Chemistry. B·Björn C G KarlssonIan A Nicholls

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