Understanding the physical and chemical nature of the warfarin drug binding site in human serum albumin: experimental and theoretical studies

Current Pharmaceutical Design
Osama K Abou-Zied

Abstract

Human serum albumin (HSA) is one of the major carrier proteins in the body and constitutes approximately half of the protein found in blood plasma. It plays an important role in lipid metabolism, and its ability to reversibly bind a large variety of pharmaceutical compounds makes it a crucial determinant of drug pharmacokinetics and pharmacodynamics. This review deals with one of the protein's major binding sites "Sudlow I" which includes a binding pocket for the drug warfarin (WAR). The binding nature of this important site can be characterized by measuring the spectroscopic changes when a ligand is bound. Using several drugs, including WAR, and other drug-like molecules as ligands, the results emphasize the nature of Sudlow I as a flexible binding site, capable of binding a variety of ligands by adapting its binding pockets. The high affinity of the WAR pocket for binding versatile molecular structures stems from the flexibility of the amino acids forming the pocket. The binding site is shown to have an ionization ability which is important to consider when using drugs that are known to bind in Sudlow I. Several studies point to the important role of water molecules trapped inside the binding site in molecular recognition and...Continue Reading

Citations

Feb 26, 2016·Luminescence : the Journal of Biological and Chemical Luminescence·Saba A J SulaimanOsama K Abou-Zied
Feb 8, 2018·The Journal of Biological Chemistry·Angélique Gajahi SoudahomeJoël Couprie
Feb 13, 2016·Physical Chemistry Chemical Physics : PCCP·Fei Ding, Wei Peng
May 31, 2020·Archives of Pharmacal Research·Nileshkumar MeghaniKyung Hyun Choi
Oct 12, 2018·Nanoscale Research Letters·Liming YuanQiufang Zhang
Nov 1, 2017·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·P Sarbadhikary, A Dube
Sep 16, 2020·Journal of Biomolecular Structure & Dynamics·Hamid Dezhampanah, Zahra Shabanzade
Nov 3, 2020·Frontiers in Molecular Biosciences·Jay V ShahVidya Ganapathy
Feb 14, 2021·Materials Science & Engineering. C, Materials for Biological Applications·R L FariasA V G Netto
Dec 4, 2019·Journal of Inorganic Biochemistry·Gislaine A da CunhaAdelino V G Netto

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