Heme impairs allosterically drug binding to human serum albumin Sudlow's site I.

Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional ligand (e.g., heme and drugs) binding capacity. Here, the binding of chlorpropamide, digitoxin, furosemide, indomethacin, phenylbutazone, sulfisoxazole, and tolbutamide to HSA and ferric heme-HSA is reported. Moreover, ferric heme binding to HSA in the absence and presence of drugs has been investigated. Values of the association equilibrium constant for drug binding to Sudlow's site I of ferric heme-HSA (ranging between 1.7 x 10(3) and 1.6 x 10(5)M(-1)) are lower by one order of magnitude than those for drug binding to ferric heme-free HSA (ranging between 1.9 x 10(4) and 1.8 x 10(6)M(-1)). According to linked functions, the value of the association equilibrium constant for heme binding to HSA decreases from 7.8 x 10(7)M(-1), in the absence of drugs to 7.0 x 10(6)M(-1), in the presence of drugs. These findings represent a clear-cut evidence for the allosteric inhibition of drug binding to HSA Sudlow's site I by the heme. According to linked functions, drugs impair allosterically heme binding to HSA. These results appear to be relevant in the drug therapy and management.