Structural Basis of Drug Recognition by Human Serum Albumin.
BACKGROUND
Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs.


OBJECTIVE
In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed.


CONCLUSION
As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.
['Leboffe|Loris|L|', 'di Masi|Alessandra|A|', 'Polticelli|Fabio|F|', 'Trezza|Viviana|V|', 'Ascenzi|Paolo|P|']
D001665:Binding Sites D006801:Humans D008024:Ligands D011485:Protein Binding D000075462:Serum Albumin, Human
structural basis drug recognition Human serum albumin allosteric modulation of drug
binding competitive modulation of drug binding drug carrier