title: Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins.
abstract: The three-dimensional structure of hanatoxin1 (HaTx1) was determined by using NMR spectroscopy. HaTx1 is a 35 amino acid residue peptide toxin that inhibits the drk1 voltage-gated K(+) channel not by blocking the pore, but by altering the energetics of gating. Both the amino acid sequence of HaTx1 and its unique mechanism of action distinguish this toxin from the previously described K(+) channel inhibitors. Unlike most other K(+) channel-blocking toxins, HaTx1 adopts an "inhibitor cystine knot" motif and is composed of two beta-strands, strand I for residues 19-21 and strand II for residues 28-30, connected by four chain reversals. A comparison of the surface features of HaTx1 with those of other gating modifier toxins of voltage-gated Ca(2+) and Na(+) channels suggests that the combination of a hydrophobic patch and surrounding charged residues is principally responsible for the binding of gating modifier toxins to voltage-gated ion channels.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: J I
authors.initials: JI
authors.lastname: Kim
authors.forename: H J
authors.initials: HJ
authors.lastname: Min
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: K J
authors.initials: KJ
authors.lastname: Swartz
authors.forename: I
authors.initials: I
authors.lastname: Shimada
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D003553:Cystine / Q000737:chemistry / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009865:Oocytes; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary; D017384:Sequence Deletion / Q000235:genetics; D012996:Solutions; D013111:Spider Venoms / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D051668:Delayed Rectifier Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012996:Solutions; D013111:Spider Venoms; D014118:Toxins, Biological; C096469:hanatoxin; D003553:Cystine