Weishan Yang and Jing Feng contributed equally to the work.
BF9, the First Functionally Characterized Snake Toxin Peptide with Kunitz-Type Protease and Potassium Channel Inhibiting Properties
Article first published online: 14 NOV 2013
© 2013 Wiley Periodicals, Inc.
Journal of Biochemical and Molecular Toxicology
Volume 28, Issue 2, pages 76–83, February 2014
How to Cite
Yang, W., Feng, J., Wang, B., Cao, Z., Li, W., Wu, Y. and Chen, Z. (2014), BF9, the First Functionally Characterized Snake Toxin Peptide with Kunitz-Type Protease and Potassium Channel Inhibiting Properties. J. Biochem. Mol. Toxicol., 28: 76–83. doi: 10.1002/jbt.21538
Contract Grant Sponsor: National Basic Research Program of China.
Contract Grant Number: 2010CB529800.
Contract Grant Sponsor: National High Technology Research and Development Program of China.
Contract Grant Number: 2012AA020304.
Contract Grant Sponsor: National Natural Sciences Foundation of China.
Contract Grant Number: 31200557.
- Issue published online: 4 FEB 2014
- Article first published online: 14 NOV 2013
- Manuscript Revised: 16 OCT 2013
- Manuscript Received: 3 AUG 2013
- National Basic Research Program of China. Grant Number: 2010CB529800
- National High Technology Research and Development Program of China. Grant Number: 2012AA020304
- National Natural Sciences Foundation of China. Grant Number: 3120055
- Snake Toxin;
- Serine Protease;
- Potassium Channel
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.