Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin

Alessio Bocedi, Stefania Notari, Enea Menegatti, Gabriella Fanali, Mauro Fasano, Paolo Ascenzi

Research output: Contribution to journalArticlepeer-review


Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional capacity to bind ligands (e.g. heme and drugs). Here, binding of the anti-HIV drugs abacavir, atazanavir, didanosine, efavirenz, emtricitabine, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, and zidovudine to HSA and ferric heme-HSA is reported. Ferric heme binding to HSA in the absence and presence of anti-HIV drugs was also investigated. The association equilibrium constant and second-order rate constant for the binding of anti-HIV drugs to Sudlow's site I of ferric heme-HSA are lower by one order of magnitude than those for the binding of anti-HIV drugs to HSA. Accordingly, the association equilibrium constant and the second-order rate constant for heme binding to HSA are decreased by one order of magnitude in the presence of anti-HIV drugs. In contrast, the first-order rate constant for ligand dissociation from HSA is insensitive to anti-HIV drugs and ferric heme. These findings represent clear-cut evidence for the allosteric inhibition of anti-HIV drug binding to HSA by the heme. In turn, anti-HIV drugs allosterically impair heme binding to HSA. Therefore, Sudlow's site I and the heme cleft must be functionally linked.

Original languageEnglish
Pages (from-to)6287-6296
Number of pages10
JournalFEBS Journal
Issue number24
Publication statusPublished - Dec 2005


  • Allostery
  • Anti-HIV drugs
  • Ferric heme
  • Human serum albumin
  • Ligand binding

ASJC Scopus subject areas

  • Biochemistry


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