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1jlp
From Proteopedia
(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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'''Solution Structure of the Noncompetitive Skeletal Muscle Nicotinic Acetylcholine Receptor Antagonist Psi-conotoxin PIIIF'''<br /> | '''Solution Structure of the Noncompetitive Skeletal Muscle Nicotinic Acetylcholine Receptor Antagonist Psi-conotoxin PIIIF'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A novel inhibitor of nicotinic acetylcholine receptors (nAChRs), psi-conotoxin Piiif, was isolated from the venom of Conus purpurascens and | + | 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== | ==About this Structure== | ||
| - | 1JLP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1JLP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JLP OCA]. |
==Reference== | ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12767216 12767216] | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12767216 12767216] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ireland, C | + | [[Category: Ireland, C M.]] |
| - | [[Category: Wagoner, R | + | [[Category: Wagoner, R M.Van.]] |
[[Category: NH2]] | [[Category: NH2]] | ||
[[Category: amidated c-terminus]] | [[Category: amidated c-terminus]] | ||
[[Category: multiple disulfide bonds]] | [[Category: multiple disulfide bonds]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:24:07 2008'' |
Revision as of 11:24, 21 February 2008
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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 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
Page seeded by OCA on Thu Feb 21 13:24:07 2008
