title: Allosteric modulation of drug binding to human serum albumin.
abstract: Human serum albumin (HSA), the most prominent protein in plasma, is best known for its extraordinary ligand binding capacity. The three homologous domains of HSA (labeled I, II, and III), each in turn composed of two subdomains (named A and B), give rise to the three-dimensional structure of HSA. This flexible structural organization allows the protein structure to adapt to a variety of ligands. As conformational adaptability of HSA extends well beyond the immediate vicinity of the binding site(s), cooperativity and allosteric modulation arise among binding sites; this makes HSA similar to a multimeric protein. Although kinetic and thermodynamic parameters for ligand binding to HSA calculated by quantitative structure-activity relationship models are in excellent agreement with those obtained in vitro, cooperative and allosteric equilibria between different binding sites and competition between drugs or between drugs and endogenous ligands make difficult the interpretation of HSA binding properties in vivo. Binding of exogenous and endogenous ligands to HSA appears to be relevant in drug therapy and management. Here, the allosteric modulation of drug binding to HSA is briefly reviewed.
authors.affiliation: Istituto Nazionale per le Malattie Infettive I.R.C.C.S. Lazzaro Spallanzani, Via Portuense 292, I-00149 Roma, Italy. ascenzi@uniroma3.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Alessio
authors.initials: A
authors.lastname: Bocedi
authors.forename: Stefania
authors.initials: S
authors.lastname: Notari
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fanali
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fesce
authors.forename: Mauro
authors.initials: M
authors.lastname: Fasano
mesh_terms: D000494:Allosteric Regulation; D006801:Humans; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D012709:Serum Albumin