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1d7t
From Proteopedia
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NMR STRUCTURE OF AN ENGINEERED CONTRYPHAN CYCLIC PEPTIDE (MOTIF CPXXPXC)
Overview
Contryphan-R, from venom of the cone-shell Conus radiatus, represents a, novel cyclic peptide scaffold onto which residues may be grafted to mimic, unrelated protein surfaces. Three substitutions were made at the x and X, positions of the disulfide-bridged motif CPxXPXC, where X and x represent, any L- and D-handed residues, respectively, P represents proline or, hydroxyproline, and C a half-cystine. These substitutions were designed to, mimic part of the pharmacophore of the unrelated globular polypeptide, omega-conotoxin GVIA, which blocks N-type calcium channels. The structure, of this engineered contryphan, YNK-contryphan-R ([D-Tyr4, Asn5, Lys7]contryphan-R), is shown to be similar to that of native contryphan-R, (Pallaghy et al., Biochemistry, 1999, Vol. 38, pp. 13553-13559), confirming that the scaffold is robust with respect to the multiple, substitutions. In particular, the alpha-beta bond vectors characterising, the orientation of the side chains relative to the backbone are similar in, contryphan-R, YNK-contryphan-R, and omega-conotoxin GVIA, which is the, required result for a scaffold-based approach to molecular design. The, solution structure of YNK-contryphan-R has an N-terminal, nonhydrogen-bonded, chain reversal centered on Hyp3-D-Trp4, and a, C-terminal type I beta-turn. A minor form due to cis-trans isomerism of, the Hyp2-Cys3 peptide bond is present in YNK-contryphan-R in a larger, proportion than in contryphan-R. It is evident, particularly from the, (3)J(HalphaHN) coupling constants, that YNK-contryphan-R is more flexible, than contryphan-R, probably due to the absence in YNK-contryphan-R of the, Pro-Trp packing present in the native molecule. Nevertheless, the, structure confirms that cyclic peptide molecular designs can achieve the, intended conformations.
About this Structure
1D7T is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
The cyclic contryphan motif CPxXPXC, a robust scaffold potentially useful as an omega-conotoxin mimic., Pallaghy PK, Norton RS, Biopolymers. 2000 Sep;54(3):173-9. PMID:10861378
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