Ligand binding to the FA3-FA4 cleft inhibits the esterase-like activity of human serum albumin

PloS One
Paolo AscenziMauro Fasano

Abstract

The hydrolysis of 4-nitrophenyl esters of hexanoate (NphOHe) and decanoate (NphODe) by human serum albumin (HSA) at Tyr411, located at the FA3-FA4 site, has been investigated between pH 5.8 and 9.5, at 22.0°C. Values of Ks, k+2, and k+2/Ks obtained at [HSA] ≥ 5×[NphOXx] and [NphOXx] ≥ 5×[HSA] (Xx is NphOHe or NphODe) match very well each other; moreover, the deacylation step turns out to be the rate limiting step in catalysis (i.e., k+3 < k+2). The pH dependence of the kinetic parameters for the hydrolysis of NphOHe and NphODe can be described by the acidic pKa-shift of a single amino acid residue, which varies from 8.9 in the free HSA to 7.6 and 7.0 in the HSA:NphOHe and HSA:NphODe complex, respectively; the pK>a-shift appears to be correlated to the length of the fatty acid tail of the substrate. The inhibition of the HSA-Tyr411-catalyzed hydrolysis of NphOHe, NphODe, and 4-nitrophenyl myristate (NphOMy) by five inhibitors (i.e., diazepam, diflunisal, ibuprofen, 3-indoxyl-sulfate, and propofol) has been investigated at pH 7.5 and 22.0°C, resulting competitive. The affinity of diazepam, diflunisal, ibuprofen, 3-indoxyl-sulfate, and propofol for HSA reflects the selectivity of the FA3-FA4 cleft. Under conditions where Tyr411 is...Continue Reading

References

Nov 4, 1975·Biochemistry·G E Means, M L Bender
Jul 1, 1978·British Journal of Clinical Pharmacology·D M RutherfordP J Tyrer
Apr 1, 1978·Clinical Pharmacology and Therapeutics·M M ReidenbergJ Cheripko
Feb 1, 1979·British Journal of Clinical Pharmacology·W H SteeleG M Baird
Nov 1, 1989·Clinical Pharmacokinetics·J Kanto, E Gepts
Jul 1, 1986·Clinical Pharmacology and Therapeutics·E M LaskaN McCormick
Nov 1, 1985·Pharmacotherapy·P MojaverianR K Ferguson
Jan 1, 1985·The Journal of International Medical Research·G M Janssen, J F Venema
Dec 1, 1971·European Journal of Biochemistry·M R HollawayM Brunori
Apr 1, 1983·Journal of Pharmaceutical Sciences·N OhtaK Ikeda
Jan 1, 1981·International Journal of Nuclear Medicine and Biology·E R Farre, Y Cohen
Jul 1, 1997·Journal of Pharmaceutical and Biomedical Analysis·V K CheruvallathJ H Perrin
Jul 2, 1999·Protein Engineering·S SugioK Kobayashi
Jun 26, 2002·Biological & Pharmaceutical Bulletin·Ulrich Kragh-HansenMasaki Otagiri
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Sep 20, 2005·Journal of Molecular Biology·Jamie GhumanStephen Curry
Oct 11, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ken-ichi KanekoMasaki Otagiri
Sep 12, 2009·Drug Metabolism and Pharmacokinetics·Stephen Curry
May 11, 2011·IUBMB Life·Gabriella FanaliMauro Fasano
Jan 11, 2012·Molecular Aspects of Medicine·Gabriella FanaliPaolo Ascenzi
May 9, 2012·Biochemical and Biophysical Research Communications·Paolo Ascenzi, Mauro Fasano
Jul 10, 2012·Biochemical and Biophysical Research Communications·Paolo AscenziMauro Fasano
Feb 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Andrew R Buller, Craig A Townsend
Jan 29, 2014·Toxins·Eric DevineHorst-Dieter Lemke
Jun 4, 2014·Basic & Clinical Pharmacology & Toxicology·Muhammad Suleman KhanChristina Eintrei

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Citations

Jan 1, 2021·Talanta·Deepak KumarDibyajyoti Banerjee

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Methods Mentioned

BETA
acetylation
deacylation
acylation

Software Mentioned

GraphPad Prism
GraphPad

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