tailieunhanh - Báo cáo khoa học: Cupiennin 1a, an antimicrobial peptide from the venom of the neotropical wandering spider Cupiennius salei, also inhibits the formation of nitric oxide by neuronal nitric oxide synthase

Cupiennin 1a (GFGALFKFLAKKVAKTVAKQAAKQGAKYVVNKQ-ME-NH2) is a potent venom component of the spider Cupiennius salei. Cupiennin 1a shows multifaceted activity. In addition to known antimicro-bial and cytolytic properties, cupiennin 1a inhibits the formation of nitric oxide by neuronal nitric oxide synthase at an IC50 concentration of ± . | ễFEBS Journal Cupiennin 1a an antimicrobial peptide from the venom of the neotropical wandering spider Cupiennius salei also inhibits the formation of nitric oxide by neuronal nitric oxide synthase Tara L. Pukala1 Jason R. Doyle2 Lyndon E. Llewellyn2 Lucia Kuhn-Nentwig3 Margit A. Apponyi1 Frances Separovic4 and John H. Bowie1 1 Department of Chemistry The University of Adelaide Australia 2 Institute of Marine Science Townsville Queensland Australia 3 ZoologicalInstitute University of Bern Switzerland 4 Schoolof Chemistry Bio21 Institute University of Melbourne Australia Keywords cupiennin 1a Cupiennius salei neuronal nitric oxide synthase activity twodimensional NMR Correspondence J. H. Bowie Department of Chemistry The University of Adelaide Adelaide SA 5005 Australia Fax 61 08 830 34358 Tel 61 08 830 3567 E-mail Received 22 August 2006 revised 17 January 2007 accepted 1 February 2007 Cupiennin 1a GFGALFKFLAKKVAKTVAKQAAKQGAKYVVNKQ-ME-NH2 is a potent venom component of the spider Cupiennius salei. Cupiennin 1a shows multifaceted activity. In addition to known antimicrobial and cytolytic properties cupiennin 1a inhibits the formation of nitric oxide by neuronal nitric oxide synthase at an IC50 concentration of pM. This is the first report of neuronal nitric oxide synthase inhibition by a component of a spider venom. The mechanism by which cupi-ennin 1a inhibits neuronal nitric oxide synthase involves complexation with the regulatory protein calcium calmodulin. This is demonstrated by chemical shift changes that occur in the heteronuclear single quantum coherence spectrum of 15N-labelled calcium calmodulin upon addition of cupien-nin 1a. The NMR data indicate strong binding within a complex of 1 1 stoichiometry. doi The neotropical wandering spider Cupiennius salei is a large nocturnal hunting spider distributed throughout Central America located as far north as Veracruz state in Mexico and extending