BF9, the first functionally characterized snake toxin peptide with Kunitz-type protease and potassium channel inhibiting properties.
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 IC₅₀ 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.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
Weishan
W
Yang
Jing
J
Feng
Bin
B
Wang
Zhijian
Z
Cao
Wenxin
W
Li
Yingliang
Y
Wu
Zongyun
Z
Chen
D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D034421:Sus scrofa; D014361:Trypsin Inhibitors / Q000494:pharmacology*
C443129:BF9 chymotrypsin inhibitor; D002038:Bungarotoxins; D050505:Mutant Proteins; D010455:Peptides; D026902:Potassium Channel Blockers; D011994:Recombinant Proteins; D014361:Trypsin Inhibitors
BF9; Kunitz-Type; Potassium Channel; Serine Protease; Snake Toxin