1cmr
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NMR SOLUTION STRUCTURE OF A CHIMERIC PROTEIN, DESIGNED BY TRANSFERRING A FUNCTIONAL SNAKE BETA-HAIRPIN INTO A SCORPION ALPHA/BETA SCAFFOLD (PH 3.5, 20C), NMR, 18 STRUCTURES
OverviewOverview
The alpha/beta scorpion fold is shared by scorpion toxins, insect, defensins, and plant thionins. This small and functionally versatile, template contains an alpha-helix and a triple beta-sheet linked by three, disulfide bridges. With the view to introduce novel functional centers, within this fold, we replaced the sequence (the cysteines and glycines, excepted) of the original beta-hairpin of a scorpion toxin by the sequence, of a beta-hairpin that forms part of the site by which snake neurotoxins, bind to nicotinic acetylcholine receptors (AcChOR). The resulting chimeric, protein, synthesized by chemical means, binds to AcChOR, though with a, lower affinity than the snake toxins [Drakopoulou; E., Zinn-Justin, S., Guenneugues, M., Gilquin, B., Menez, A., & Vita, C. (1996) J. Biol. Chem., 271, 11979-11987]. The work described in this paper is an attempt to, clarify the structural consequences associated with the transfer of the, beta-hairpin. We report the determination of the three-dimensional, solution structure of the chimeric protein by proton NMR spectroscopy and, molecular dynamics calculations. Comparison of the structure of the, chimera with those of the scorpion alpha/beta toxin and of the snake, neurotoxin shows that (i) the new protein folds as an alpha/beta motif and, (ii) the beta-hairpins of the chimera and of the curaremimetic toxin adopt, a similar conformation. A closer inspection of the differences between the, structures of the original and transferred beta-hairpins allows, rationalization of the biological properties of the chimera.
About this StructureAbout this Structure
1CMR is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Transfer of a beta-hairpin from the functional site of snake curaremimetic toxins to the alpha/beta scaffold of scorpion toxins: three-dimensional solution structure of the chimeric protein., Zinn-Justin S, Guenneugues M, Drakopoulou E, Gilquin B, Vita C, Menez A, Biochemistry. 1996 Jul 2;35(26):8535-43. PMID:8679614
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