Premium
ImKTx1, a new Kv1.3 channel blocker with a unique primary structure
Author(s) -
Chen Zongyun,
Hu Youtian,
Han Song,
Yin Shijin,
He Yawen,
Wu Yingliang,
Cao Zhijian,
Li Wenxin
Publication year - 2011
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20382
Subject(s) - peptide , spider toxin , scorpion toxin , venom , protein primary structure , scorpion venoms , scorpion , channel blocker , peptide sequence , chemistry , ion channel , recombinant dna , biochemistry , biology , microbiology and biotechnology , gene , receptor , glutamate receptor , organic chemistry , calcium
Toxins from the venoms of scorpion, snake, and spider are valuable tools to probe the structure–function relationship of ion channels. In this investigation, a new toxin gene encoding the peptide ImKTx1 was isolated from the venom gland of the scorpion Isometrus maculates by constructing cDNA library method, and the recombinant ImKTx1 peptide was characterized physiologically. The mature peptide of ImKTx1 has 39 amino acid residues including six cross‐linked cysteines. The electrophysiological experiments showed that the recombinant ImKTx1 peptide had a pharmacological profile where it inhibited Kv1.3 channel currents with IC 50 of 1.70 n± 1.35 µM, whereas 10 µM rImKTx1 peptide inhibited about 40% Kv1.1 and 42% Kv1.2 channel currents, respectively. In addition, 10 µM rImKTx1 had no effect on the Nav1.2 and Nav1.4 channel currents. Multiple sequence alignments showed that ImKTx1 had no homologous toxin peptide, but it was similar with Ca 2+ channel toxins from scorpion and spider in the arrangement of cysteine residues. These results indicate that ImKTx1 is a new Kv1.3 channel blocker with a unique primary structure. Our results indicate the diversity of K + channel toxins from scorpion venoms and also provide a new molecular template targeting Kv1.3 channel. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:244–251, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20382