Journal of University of Chinese Academy of Sciences >
Crystal Structures of Neurotoxins Bmk M1 and M4 from Chinese Scorpion Buthus martensii Karsch
Received date: 2001-05-24
Online published: 2001-01-10
Three bioactivity variant neurotoxins, BmK M1, M4 and M8, have been purified from venom of the Chinese scorpion Buthus martensii Karsch. They possess distinct toxic activity on mice in vivo with different electrostatic properties. The relative toxicities of BmK M1, M4 and M8 are 13.3:2.5:1, which interestingly correspond to their respective pI values, ranging from basic to acidic, of 9.01, 7.53 and 5.30. In addition, the BmK M1 and M4 belong to α like toxin, while the BmK M8 belongs to classical α toxin so that they may bind to Na + channel at different microsite. The crystal structures of BmK M1, M4 have been determined and refined at resolutions 0.17 nm (M1), 0.13 nm (M4), respectively. The structure investigations in association with the site mutagenesis experiments revealed three significant surface areas: Face A and B relevant to the toxic potency expression; Site RC involved in the receptor binding specificity. Interestingly the substitutions with negative charge potentid residues in the Face B will dramatically reduce the toxic activity of the molecule, which suggested a "Charge potential mediated mechanism" for toxicity expression. Based on the high resolution structure, the most interesting finding is a unusual non prolyl cis peptide bond (residue 9～10) appeared in the site relative to receptor binding of the α like toxin BmK M1 and M4, but not in the classical α toxin BmK M8. The observations provide a possible structural basis for the α like toxin receptor binding site selectivity and propose a " cis peptide bond mediated mechanism" for the toxin receptor binding specificity. This manifested a way to achieve high levels of molecular specificity through the strained backbone geometry.
He Xiaolin , Wang Dacheng . Crystal Structures of Neurotoxins Bmk M1 and M4 from Chinese Scorpion Buthus martensii Karsch[J]. Journal of University of Chinese Academy of Sciences, 2001 , 18(1) : 97 -100 . DOI: 10.7523/j.issn.2095-6134.2001.1.015
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