TY - JOUR
T1 - Heme impairs allosterically drug binding to human serum albumin Sudlow's site I
AU - Ascenzi, Paolo
AU - Bocedi, Alessio
AU - Notari, Stefania
AU - Menegatti, Enea
AU - Fasano, Mauro
PY - 2005/8/26
Y1 - 2005/8/26
N2 - 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 × 103 and 1.6 × 105 M-1) are lower by one order of magnitude than those for drug binding to ferric heme-free HSA (ranging between 1.9 × 104 and 1.8 × 106 M -1). According to linked functions, the value of the association equilibrium constant for heme binding to HSA decreases from 7.8 × 10 7 M-1, in the absence of drugs to 7.0 × 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.
AB - 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 × 103 and 1.6 × 105 M-1) are lower by one order of magnitude than those for drug binding to ferric heme-free HSA (ranging between 1.9 × 104 and 1.8 × 106 M -1). According to linked functions, the value of the association equilibrium constant for heme binding to HSA decreases from 7.8 × 10 7 M-1, in the absence of drugs to 7.0 × 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.
KW - Allostery
KW - Drugs
KW - Ferric heme
KW - Ferric heme-human serum albumin
KW - Human serum albumin
KW - Ligand binding
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U2 - 10.1016/j.bbrc.2005.06.127
DO - 10.1016/j.bbrc.2005.06.127
M3 - Article
C2 - 16004963
AN - SCOPUS:22144459777
VL - 334
SP - 481
EP - 486
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -