- 作者: 楊振忠
- 作者服務機構: 清華大學生命科學研究所
- 中文摘要:
A historical review on the study of snake neurotoxins is presented, with special emphasis on the author's contributions in unraveling the chemistry of one of the most lethal non-enzymatic protein factors. Cobrotoxin, a postsynaptic neurotoxin isolated in a crystalline state from the venom of Taiwan cobra, binds specifically to the nicotinic acetylcholine receptors on the postsynaptic membrane and thus blocks the neuromuscular transmission. It is a small basic protein consisting of a single peptide chain of 62 amino-acid residues, crosslinked by four disulfide bonds. The disulfide bonds and Tyr-25 which are buried in the molecule form a central core to maintain and stabilize the active conformation of the toxin. Selective and stepwise chemical modifications of cobrotoxin indicate that at least two cationic groups, an .epsilon.-amino group of Lys-47 and a guanidino group of Arg-33, both of which are common to all known postsynaptic snake neurotoxins, held at a certain critical distance in the molecule, are functionally important for its neuromuscular blocking activity.
Neurotoxins of another type exist in some common cobras or sea snakes. These presynaptic neurotoxins are basic phospholipase A/sub 2/ (PLA /sub 2/) per se or contain basic PLA/sub 2/ as an indispensable part of their structures. Presynaptic PLA/sub 2/ neurotoxins show both PLA/sub 2/ activity and presynaptic neurotoxicity. Chemical modification of two highly potent presynaptic neurotoxins,.beta./sub 1/-bungarotoxin and notexin was undertaken in the hope of elucidating the molecular features contributing to the biological activities of presynaptic PLA/sub 2/ neurotoxins. Modification of tyrosine residues differentially influences the enzymatic activity and lethal toxicity of .beta./sub 1/-bungarotoxin and notexin, revealing that these toxins might possess two functional sites, one being responsible for the catalytic activity and the other for their pharmacological properties. - 英文摘要: --
- 中文關鍵字: Snake Venom; Neurotoxin; Cobra; Chemistry; Catalytic Activity; Pharmacology
- 英文關鍵字: 蛇毒;神經毒素;眼鏡蛇;化學;觸媒活性;藥理學