tailieunhanh - Báo cáo khoa học: Allosteric modulation of myristate and Mn(III)heme binding to human serum albumin Optical and NMR spectroscopy characterization

Human serum albumin (HSA) is best known for its extraordinary ligand binding capacity. HSA has a high affinity for heme and is responsible for the transport of medium and long chain fatty acids. Here, we report myri-state binding to the N and B conformational states of Mn(III)heme–HSA (. at pH and , respectively) as investigated by optical absorbance and NMR spectroscopy. At pH , Mn(III)heme binds to HSA with lower affinity than Fe(III)heme, and displays a water molecule coordinated to the metal | iFEBS Journal Allosteric modulation of myristate and Mn III heme binding to human serum albumin Optical and NMR spectroscopy characterization Cnahriolla Fanali1 Rirrar do Focr o1 rĩc ĩna Aoim Ĩ1 Panin Acnrairzi2 3 Maiim Pacann1 JaUl Iclla roll Idll lilCbaKJU rcsce wIISLII la HyiaU r auiu Hoccuz aiiM Iviauiu rasaHU 1 Dipartimento di Biologia Strutturale e Funzionale and Centro di Neuroscienze Universita dell Insubria Busto Arsizio VA Italy 2 Dipartimento di Biologia and Laboratorio Interdisciplinare di Microscopia Elettronica Universita Roma Tre Italy 3 Istituto Nazionale per le Malattie Infettive . Lazzaro Spallanzani Roma Italy Keywords allostery fatty acid binding heme binding human serum albumin NMR relaxation Correspondence M. Fasano Dipartimento di Biologia Strutturale e Funzionale Universita dell Insubria Via Alberto da Giussano 12 I-21052 Busto Arsizio VA Italy Fax 39 0331 339459 Tel 39 0331 339450 E-mail Website http cns fasano Received 21 April2005 revised 25 July 2005 accepted 26 July 2005 doi Human serum albumin HSA is best known for its extraordinary ligand binding capacity. HSA has a high affinity for heme and is responsible for the transport of medium and long chain fatty acids. Here we report myristate binding to the N and B conformational states of Mn III heme-HSA . at pH and respectively as investigated by optical absorbance and NMR spectroscopy. At pH Mn III heme binds to HSA with lower affinity than Fe III heme and displays a water molecule coordinated to the metal. Myristate binding to a secondary site FAx allosterically coupled to the heme site not only increases optical absorbance of Mn III heme-bound HSA by a factor of approximately three but also increases the Mn III -heme affinity for the fatty acid binding site FA1 by 10-500-fold. Cooperative binding appears to occur at FAx and accessory myristate binding sites. The .