title: 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.
abstract: Cupiennin 1a (GFGALFKFLAKKVAKTVAKQAAKQGAKYVVNKQME-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 1.3 +/- 0.3 microM. This is the first report of neuronal nitric oxide synthase inhibition by a component of a spider venom. The mechanism by which cupiennin 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 cupiennin 1a. The NMR data indicate strong binding within a complex of 1 : 1 stoichiometry.
authors.affiliation: Department of Chemistry, The University of Adelaide, Australia.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Pukala
authors.forename: Jason R
authors.initials: JR
authors.lastname: Doyle
authors.forename: Lyndon E
authors.initials: LE
authors.lastname: Llewellyn
authors.forename: Lucia
authors.initials: L
authors.lastname: Kuhn-Nentwig
authors.forename: Margit A
authors.initials: MA
authors.lastname: Apponyi
authors.forename: Frances
authors.initials: F
authors.lastname: Separovic
authors.forename: John H
authors.initials: JH
authors.lastname: Bowie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D013111:Spider Venoms / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013112:Spiders / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D002147:Calmodulin; D004791:Enzyme Inhibitors; D010455:Peptides; D013111:Spider Venoms; C453880:cupiennin 1a; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D002118:Calcium