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Báo cáo khoa học: Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin
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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, 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 IVIciicyai.il jauiieiia raiiaii Iviauio ra aiiu and Paolo Ascenzi1 1 National institute for Infectious Diseases I.R.C.C.S. 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@bio.uniroma3.it Note These authors contributed equally to this work. Received 29 August 2005 revised 4 October 2005 accepted 13 October 2005 doi 10.1111 j.1742-4658.2005.05015.x 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 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 .