tailieunhanh - Báo cáo khoa học: Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin

Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional capacity to bind ligands (. heme and drugs). Here, binding of the anti-HIV drugs abacavir, atazanavir, didano-sine, efavirenz, emtricitabine, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, and zidovudine to HSA and ferric heme–HSA is reported. | ềFEBS Journal Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin AIoqqỉo Rr norl11 Q ofan19 Nntari1 Fnoa Monoriat i2 ftahriolla Fanali3 l lai ir - Facann3 Micooiu DvUcui otciana IMULaii cIlea jauiieiia raiiaii Iviauio ra aiiu and Paolo Ascenzi1 1 National institute for Infectious Diseases . Lazzaro Spallanzani Roma Italy 2 Department of PharmaceuticalSciences University of Ferrara Italy 3 Department of Structuraland FunctionalBiology University of Insubria Busto Arsizio VA Italy Keywords allostery anti-HIV drugs ferric heme human serum albumin ligand binding Correspondence P. Ascenzi Department of Biology and InterdepartmentalLaboratory for Electron Microscopy University Roma Tre Viale Guglielmo Marconi 446 I-00146 Roma Italy Fax 39 06 55176321 Tel 39 06 55173200 2 E-mail ascenzi@ Note These authors contributed equally to this work. Received 29 August 2005 revised 4 October 2005 accepted 13 October 2005 doi Human serum albumin HSA the most prominent protein in plasma is best known for its exceptional capacity to bind ligands . heme and drugs . Here binding of the anti-HIV drugs abacavir atazanavir didano-sine 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 antiHIV 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 antiHIV drugs. In contrast the first-order rate constant for ligand dissociation from HSA is insensitive to anti-HIV drugs and .