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1jlp
From Proteopedia
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|GENE= | |GENE= | ||
|DOMAIN= | |DOMAIN= | ||
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jlp OCA], [http://www.ebi.ac.uk/pdbsum/1jlp PDBsum | + | |RELATEDENTRY=[[1as5|1AS5]], [[1jlo|1JLO]] |
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jlp OCA], [http://www.ebi.ac.uk/pdbsum/1jlp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jlp RCSB]</span> | ||
}} | }} | ||
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[[Category: multiple disulfide bond]] | [[Category: multiple disulfide bond]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:35:30 2008'' |
Revision as of 18:35, 30 March 2008
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| Ligands: | , | ||||||
| Related: | 1AS5, 1JLO
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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]. 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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