1jlp
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(New page: 200px<br /><applet load="1jlp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jlp" /> '''Solution Structure of the Noncompetitive Ske...)
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Revision as of 16:14, 20 November 2007
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Solution Structure of the Noncompetitive Skeletal Muscle Nicotinic Acetylcholine Receptor Antagonist Psi-conotoxin PIIIF
Overview
A novel inhibitor of nicotinic acetylcholine receptors (nAChRs), psi-conotoxin Piiif, was isolated from the venom of Conus purpurascens and, found to have the sequence GOOCCLYGSCROFOGCYNALCCRK-NH2. The sequence is, highly homologous to that of psi-conotoxin Piiie, a previously identified, noncompetitive inhibitor of Torpedo electroplax nAChR, also isolated from, C. purpurascens. Both psi-conotoxins block Torpedo and mouse nicotinic, acetylcholine receptors (nAChRs), but psi-Piiif is less potent by a factor, of 10(1)-10(2). A high-resolution structure of psi-Piiif was determined by, NMR and molecular modeling calculations. Psi-Piiif analogues containing, [(13)C]-labeled cysteine at selected positions were synthesized to resolve, spectral overlap of Cys side chain proton signals. The structures are, well-converged, with backbone atom position RMSDs of 0.21 A for the main, body of the peptide between residues 4 and 22 and 0.47 A for all residues., The overall backbone conformation is closely similar to psi-Piiie, the, main difference being in the degree of conformational disorder at the two, termini. Psi-Piiie and psi-Piiif have similar locations of positive charge, density, although psi-Piiif has a lower overall charge. One disulfide, bridge of psi-Piiif appears to undergo dynamic conformational fluctuations, based on both the model and on experimental observation. Chimeras in which, the three intercysteine loops were swapped between psi-Piiie and psi-Piiif, were tested for inhibitory activity against Torpedo nAChRs. The third, loop, which contains no charged residues in either peptide, is the prime, determinant of potency in these psi-conotoxins.
About this Structure
1JLP is a Single protein structure of sequence from [1] with NH2 as ligand. Full crystallographic information is available from OCA.
Reference
Characterization and three-dimensional structure determination of psi-conotoxin Piiif, a novel noncompetitive antagonist of nicotinic acetylcholine receptors., Van Wagoner RM, Jacobsen RB, Olivera BM, Ireland CM, Biochemistry. 2003 Jun 3;42(21):6353-62. PMID:12767216
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