tailieunhanh - Báo cáo khoa học: Modulation of heme and myristate binding to human serum albumin by anti-HIV drugs An optical and NMR spectroscopic study

Human serum albumin (HSA) has an extraordinary ligand-binding capac-ity, and transports Fe(III)heme and medium- and long-chain fatty acids. In human immunodeficiency virus-infected patients the administered drugs bind to HSA and act as allosteric effectors. Here, the binding of Fe(III)-heme to HSA in the presence of three representative anti-HIV drugs and myristate is investigated. | ỊFEBS Journal Modulation of heme and myristate binding to human serum albumin by anti-HIV drugs An optical and NMR spectroscopic study Gabriella Fanali1 Alessio Bocedi2 3 Paolo Ascenzi2 3 and Mauro Fasano1 1 Dipartimento di Biologia Strutturale e Funzionale and Centro di Neuroscienze Universita dell Insubria Busto Arsizio Italy 2 Istituto Nazionale per le Malattie Infettive . Lazzaro Spallanzani Rome Italy 3 Dipartimento di Biologia and Laboratorio Interdisciplinare di Microscopia Elettronica Universita Roma Tre Rome Italy Keywords allosteric modulation anti-HIV drugs heterotropic interactions human serum albumin NMR relaxation Correspondence M. Fasano Dipartimento di Biologia Strutturale e Funzionale and Centro di Neuroscienze Universita dell Insubria Via Alberto da Giussano 12 I-21052 Busto Arsizio VA Italy Fax 39 0331 339459 Tel 39 0331 339450 E-mail Present address Istituto di Ricerche di Biologia Molecolare P. Angeletti Rome Italy Received 27 February 2007 revised 20 June 2007 accepted 5 July 2007 doi Human serum albumin HSA has an extraordinary ligand-binding capacity and transports Fe III heme and medium- and long-chain fatty acids. In human immunodeficiency virus-infected patients the administered drugs bind to HSA and act as allosteric effectors. Here the binding of Fe III -heme to HSA in the presence of three representative anti-HIV drugs and myristate is investigated. Values of the dissociation equilibrium constant Kd for Fe III heme binding to HSA were determined at different myristate concentrations in the absence and presence of anti-HIV drugs. Nuclear magnetic relaxation dispersion profiles of HSA-Fe III heme were measured at different myristate concentrations in the absence and presence of anti-HIV drugs. Structural bases for anti-HIV drug binding to HSA are provided by automatic docking simulation. Abacavir and nevirapine bind to HSA with Kd values of 1 X 10-6 and 2 X 10-6 M .