Allostery in a monomeric protein: the case of human serum albumin.

Human serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites. HSA provides a depot for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites. Its modular domain organization provides a variety of ligand-binding sites and the flexible modular structure involves more than the immediate vicinity of the binding site(s), affecting the ligand-binding properties of the full protein. Ferric human serum heme–albumin (heme– HSA) shows a peculiar spectroscopic properties that allow to investigate structural and functional aspects of the protein. Here, a characterization of the environment of the metal binding site and of its dynamics is reported. Moreover, the effect of different endogenous and exogenous ligands on the allosteric properties of HSA and link between binding sites are investigated. As a whole, the complex mechanism modulating ligand binding to HAS represents one of the most important structure-function correlations ever reported for monomeric proteins in general.