title: A cross-over inhibitor of the botulinum neurotoxin light chain B: a natural product implicating an exosite mechanism of action.
abstract: Clostridium botulinum produces the most lethal toxins known to man, as such they are high risk terrorist threats, and alarmingly there is no approved therapeutic. We report the first cross-over small molecule inhibitor of these neurotoxins and propose a mechanism by which it may impart its inhibitory activity.
authors.affiliation: Department of Chemistry, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Salzameda
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Eubanks
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Zakhari
authors.forename: Kyoji
authors.initials: K
authors.lastname: Tsuchikama
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: DeNunzio
authors.forename: Karen N
authors.initials: KN
authors.lastname: Allen
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hixon
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000595:Amino Acid Sequence; D001688:Biological Products / Q000494:pharmacology* / Q000627:therapeutic use; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D020134:Catalytic Domain; D003014:Clostridium botulinum / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D019428:HIV Integrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*; D050825:Synaptosomal-Associated Protein 25 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D001688:Biological Products; D002109:Caffeic Acids; D003432:Cross-Linking Reagents; D019428:HIV Integrase Inhibitors; D009498:Neurotoxins; D013386:Succinates; D050825:Synaptosomal-Associated Protein 25; D050988:Vesicle-Associated Membrane Protein 2; D001905:Botulinum Toxins; C100435:chicoric acid