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NMR Sequential Assignments and Solution Structure of Chlorotoxin, A Small Scorpion Toxin that Blocks Chloride Channels

By Guy Lippens, Jamila Najib and Andre Tartar

Abstract

The solution structure of chlorotoxin, a small toxin purified from the venom of the Leiurus quinquestriatus scorpion, has been determined using 2D 1H NMR spectroscopy. Analysis of the NMR data shows that the structure consists of a small three-stranded antiparallel β-sheet packed against an α-helix, thereby adopting the same fold as charybdotoxin and other members of the short scorpion toxin family [Arsenievet al. (1984) FEBS Lett. 165, 57-62; Martins et al. (1990) FEBS Lett. 260, 249-253; Bontems et al. (1991) Science 254, 1521-1523]. Three disulfide bonds of chlorotoxin (Cys5-Cys28, Cys16—Cys33, and Cys20—Cys35), cross-linking the α-helix to the β-sheet, follow the common pattern found in the other short scorpion toxins. The fourth disulfide bridge (Cys2—Cys19) links the small N-terminal β strand to the rest of the molecule, in contrast to charybdotoxin where this disulfide bridge is absent and the first strand interacts with the rest of the molecule by several contacts between hydrophobic residues. Another structural difference between chlorotoxin and charybdotoxin is observed at the level of the α-β turn. This difference is accompanied by a change in the electrostatic potential surface, which is largely positive at the level of this turn in chlorotoxin, whereas no such positive potential surface can be found at the same position in charybdotoxin. In the latter protein, the positive surface is formed by different charged residues situated on the solvent-exposed site of the C-terminal β-sheet. This positive region is disrupted in chlorotoxin by the mutation of one of the arginines into a leucine and by the presence of two aspartic acid residues on the α-helix. © 1995, American Chemical Society. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Topics: Biochimie
Publisher: 'American Chemical Society (ACS)'
Year: 1995
DOI identifier: 10.1021/bi00001a003
OAI identifier: oai:dipot.ulb.ac.be:2013/261833
Provided by: DI-fusion
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