Three-Dimensional Structure of -Conotoxin PVIIA, a Novel Potassium Channel-Blocking Toxin from Cone Snails

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• 作者：Philippe Savarin ; Marc Guenneugues ; Bernard Gilquin ; Hung Lamthanh ; Sylvaine Gasparini ; Sophie Zinn-Justin ; and André ; Mé ; nez
• 刊名：Biochemistry
• 出版年：1998
• 出版时间：April 21, 1998
• 年：1998
• 卷：37
• 期：16
• 页码：5407 - 5416
• 全文大小：221K
• 年卷期：v.37,no.16(April 21, 1998)
• ISSN：1520-4995

文摘

-Conotoxin PVIIA from the venom of Conuspurpurascens is the first cone snail toxinthatwas described to block potassium channels. We synthesizedchemically this toxin and showed that itsdisulfide bridge pattern is similar to those of - and-conotoxins. -conotoxin competes withradioactive-dendrotoxin for binding to rat brain synaptosomes, confirming itscapacity to bind to potassium channels;however, it behaves as a weak competitor. The three-dimensionalstructure of -conotoxin PVIIA, aselucidated by NMR spectroscopy and molecular modeling, comprises twolarge parallel loops stabilizedby a triple-stranded antiparallel -sheet and three disulfidebridges. The overall fold of -conotoxin issimilar to that of calcium channel-blocking -conotoxins but differsfrom those of potassium channel-blocking toxins from sea anemones, scorpions, and snakes. Localtopographies of -conotoxin PVIIAthat might account for its capacity to recognize Kv1-type potassiumchannels are discussed.