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BF9, the First Functionally Characterized Snake Toxin Peptide with Kunitz‐Type Protease and Potassium Channel Inhibiting Properties
Author(s) -
Yang Weishan,
Feng Jing,
Wang Bin,
Cao Zhijian,
Li Wenxin,
Wu Yingliang,
Chen Zongyun
Publication year - 2014
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.21538
Subject(s) - chemistry , toxin , protease , peptide , potassium channel , potassium , biochemistry , biophysics , biology , enzyme , organic chemistry
ABSTRACT Although numerous Kunitz‐type toxins were isolated from snake venom, no bifunctional Kunitz‐type snake toxins with protease and potassium channel inhibiting properties have been reported till now. With the help of bioinformatics analyses and biological experiments, we characterized Kunitz‐type snake toxin BF9 as a bifunctional peptide. Enzyme and inhibitor reaction kinetics experiments showed that BF9 inhibited α‐chymotrypsin with Ki value of 1.8 × 10 −8 M. Electrophysiological experiments showed that BF9 inhibited the Kv1.3 potassium channel with an IC 50 of 120.0 nM, which demonstrated that serine protease inhibitor BF9 could also inhibit potassium channels. In addition, the key amino acids of BF9 responsible for the unique bifunctional mechanism are further investigated. To the best of our knowledge, BF9 is the first Kunitz‐type snake peptide with the unique bifunctionality of potassium channel and serine protease inhibiting properties, providing novel insights into divergent evolution and functional applications of snake Kunitz‐type peptides.