Solution structure of IsTX. A male scorpion toxin from Opisthacanthus madagascariensis (Ischnuridae).
The novel sex-specific potassium channel inhibitor IsTX, a 41-residue peptide, was isolated from the venom of male Opisthacanthus madagascariensis. Two-dimensional NMR techniques revealed that the structure of IsTX contains a cysteine-stabilized alpha/beta-fold. IsTX is classified, based on its sequential and structural similarity, in the scorpion short toxin family alpha-KTx6. The alpha-KTx6 family contains a single alpha-helix and two beta-strands connected by four disulfide bridges and binds to voltage-gated K(+) channels and apamin-sensitive Ca(2+)-activated K(+) channels. The three-dimensional structure of IsTX is similar to that of Heterometrus spinifer toxin (HsTX1). HsTX1 blocks the Kv1.3 channel at picomolar concentrations, whereas IsTX has much lower affinities (10 000-fold). To investigate the structure-activity relationship, the geometry of sidechains and electrostatic surface potential maps were compared with HsTX1. As a result of the comparison of the primary structures, Lys27 of IsTX was conserved at the same position in HsTX1. The analogous Lys23 of HsTX1, the most critical residue for binding to potassium channels, binds to the channel pore. However, IsTX has fewer basic residues to interact with acidic channel surfaces than HsTX1. MALDI-TOF MS analysis clearly indicated that IsTX was found in male scorpion venom, but not in female. This is the first report that scorpion venom contains sex-specific compounds.
Yamaji
Nahoko
N
Suntory Institute for Bioorganic Research, Mishima-Gun, Osaka 618-8503, Japan. yamaji@sunbor.or.jp
Dai
Li
L
Sugase
Kenji
K
Andriantsiferana
Marta
M
Nakajima
Terumi
T
Iwashita
Takashi
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D051664:Kv1.3 Potassium Channel; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D026902:Potassium Channel Blockers / Q000737:chemistry*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology; D012605:Scorpions / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012737:Sex Factors; D012996:Solutions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry*
C493187:IsTX toxin, Opisthacanthus madagascariensis; D051664:Kv1.3 Potassium Channel; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D012996:Solutions; C109471:TX1 toxin, Heterometrus spinnifer; D014118:Toxins, Biological