Effect of prototypic drugs ibuprofen and warfarin on global chaotropic unfolding of human serum heme-albumin: A fast-field-cycling 1H-NMR relaxometric study

Gabriella Fanali, Paolo Ascenzi, Mauro Fasano

Research output: Contribution to journalArticlepeer-review

Abstract

Human serum albumin (HSA) is the most prominent protein in plasma, but it is also found in tissues and secretions throughout the body. The three-domain design of HSA provides a variety of binding sites for many ligands, including heme and drugs. HSA has been used as a model multidomain protein to investigate how interdomain interactions affect the global folding/unfolding process. Here, we report on the reversible chemical denaturation of heme-HSA involving three different conformational states (F, N, and B, occurring at pH 4.0, 7.0, and 9.0, respectively) and on the effect of prototypic drugs ibuprofen and warfarin on thermodynamics of the reversible unfolding process. Chaotropic unfolding of heme-HSA in the F, N, and B conformations is governed by different thermodynamic regimes, with the B form showing an entropic stabilization of the structure that compensates an enthalpic destabilization, and the F form easily unfolding under entropic control. Warfarin and ibuprofen binding stabilizes heme-HSA in both N and B states.

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalBiophysical Chemistry
Volume129
Issue number1
DOIs
Publication statusPublished - Aug 2007

Keywords

  • H NMR relaxometry
  • Human serum heme-albumin
  • Ibuprofen
  • Unfolding
  • Warfarin

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Biophysics

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