Molecular cloning and functional identification of a new K(+) channel blocker, LmKTx10, from the scorpion Lychas mucronatus.
Scorpions have a venom gland which is an important determinant in contributing to their successful survival for more than 400 million years. Their venoms contain a diversity of neurotoxins, which represent a tremendous hitherto partially unexplored resource not only for understanding ion channels but also for use in drug design and development. In this investigation, LmKTx10, a new toxin gene was identified from the venom of the scorpion Lychas mucronatus by constructing cDNA library method, and its product was expressed and characterized physiologically. The mature peptide has 38 residues including six conserved cysteines. The electrophysiological experiments further indicated that the recombinant LmKTx10 peptide has an interesting pharmacological profile: it blocks Kv1.3 channel with IC(50)=28nM which is moderate Kv1.3 channel blocking activity compared to the other a-KTxs toxins, and exhibits good selectivity on Kv1.3 over Kv1.1 and Kv1.2, about 60 folds and 450 folds, respectively. These data not only enrich the family of K(+) channel toxins from scorpion venoms but also present a potential drug template for selectively targeting the Kv1.3 channel.
Liu
Jun
J
Wuhan University, People's Republic of China.
Ma
Yibao
Y
Yin
Shijin
S
Zhao
Ruiming
R
Fan
Shaozhong
S
Hu
Youtian
Y
Wu
Yingliang
Y
Cao
Zhijian
Z
Li
Wenxin
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000187:drug effects*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D017931:DNA Primers; C542560:KTx10 protein, Lychas mucronatus; D015221:Potassium Channels; D011994:Recombinant Proteins; D012604:Scorpion Venoms