Drug binding to Sudlow's site i impairs allosterically human serum heme-albumin-catalyzed peroxynitrite detoxification

Paolo Ascenzi, Alessandro Bolli, Francesca Gullotta, Gabriella Fanali, Mauro Fasano

Research output: Contribution to journalArticlepeer-review

Abstract

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 NO3- 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.

Original languageEnglish
Pages (from-to)776-780
Number of pages5
JournalIUBMB Life
Volume62
Issue number10
DOIs
Publication statusPublished - Oct 2010

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics

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