title: Sequence-specific 1H-NMR assignment and secondary structure of black mamba dendrotoxin I, a highly selective blocker of voltage-gated potassium channels.
abstract: The secondary structure of dendrotoxin I, an important constituent of the venom of the African black mamba snake Dendroaspis polylepis polylepis, was determined in aqueous solution by two-dimensional methods. Complete sequence-specific 1H-NMR assignment was obtained with the exception of the backbone amide proton of Gly39 and Cys40. Dendrotoxin I is based on a central antiparallel beta-sheet and two small helices located at the N- and the C-terminal extremities. These secondary-structural units occur at exactly the same places in the amino acid sequence as those of bovine pancreatic trypsin inhibitor (BPTI), with which dendrotoxin I shares 33% sequence similarity. According to the disulfide-bridge positions and the long-range NOE observed these secondary-structural elements fold in a similar manner to BPTI. This similarity allows an hypothesis according to which dendrotoxin I could derive from an ancestral Künitz-type proteinase inhibitor. This ancestor would have been heavily mutated at amino acid positions not critical for gross structure. The spatial locations of the solvent-exposed amino acids concerned could therefore serve as a guideline for interpretation of the structure/activity relationship of dendrotoxin I for the blockage of voltage-sensitive potassium channels of which dendrotoxin I is a strong inhibitor. The possible connections with other polypeptide toxins that block related ion currents is discussed.
authors.affiliation: Institut de Biologie Structurale, Grenoble, France.
authors.forename: M F
authors.initials: MF
authors.lastname: Foray
authors.forename: J M
authors.initials: JM
authors.lastname: Lancelin
authors.forename: M
authors.initials: M
authors.lastname: Hollecker
authors.forename: D
authors.initials: D
authors.lastname: Marion
mesh_terms: D000595:Amino Acid Sequence; D007611:Aprotinin / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D004546:Elapid Venoms / Q000737:chemistry*; D004594:Electrophysiology; D015640:Ion Channel Gating; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry*; D015221:Potassium Channels / Q000187:drug effects*; D017433:Protein Structure, Secondary
chemical_list: D004220:Disulfides; D004546:Elapid Venoms; D009498:Neurotoxins; D015221:Potassium Channels; C020273:dendrotoxin; D007611:Aprotinin