Drug Binding to Sudlow's Site I Impairs Allosterically Human Serum Heme-Albumin-Catalyzed Peroxynitrite Detoxification

作者：Ascenzi Paolo^*; Bolli Alessandro; Gullotta Francesca; F****i Gabriella; Fasano Mauro

来源：IUBMB Life, 2010, 62(10): 776-780.

DOI：10.1002/iub.381

• human serum heme-albumin
• peroxynitrite isomerization
• drug binding to Sudlow's site I
• kinetics
• allosteric inhibition

Heme endows human serum albumin (HSA) with globin-like reactivity and spectroscopic properties. Here, the effect of chlorpropamide, digitoxin, furosemide, indomethacin, phenylbutazone, sulfisoxazole, tolbutamide, and warfarin on peroxynitrite isomerization to NO(3)(-) by ferric HSA-heme (HSA-heme-Fe(III)) is reported. Drugs binding to Sudlow's site I impair dose-dependently peroxynitrite isomerization by HSA-heme-Fe(III). The allosteric modulation of HSA-heme-Fe(III)-mediated peroxynitrite isomerization by drugs has been ascribed to the pivotal role of Tyr150, a residue that either provides a polar environment in Sudlow's site I or protrudes into the heme cleft (i.e., the fatty acid site 1, FA1), depending on ligand occupancy of either sites.

• 出版日期2010-10