中国马氏钳蝎神经毒素BmK M1和M4的晶体结构研究  

Crystal Structures of Neurotoxins Bmk M1 and M4 from Chinese Scorpion Buthus martensii Karsch

作　　者：何小林[1] 王大成[1] 

机构地区：[1]中国科学院生物物理研究所,北京100101

出　　处：《中国科学院研究生院学报》2001年第1期97-100,共4页Journal of the Graduate School of the Chinese Academy of Sciences

基　　金：国家"8 63"计划 ( 10 3 13 0 1 0 6);自然科学基金 ( 39970 15 8)资助项目

摘　　要：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.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.

关 键 词：马氏钳蝎 神经毒素 晶体结构 结构-功能关系 

分 类 号：R996.3[医药卫生—毒理学]