1jlp: Difference between revisions

Line 1:

[[Image:1jlp.gif|left|200px]]<br /><applet load="1jlp" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1jlp.gif|left|200px]]<br /><applet load="1jlp" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1jlp" />

'''Solution Structure of the Noncompetitive Skeletal Muscle Nicotinic Acetylcholine Receptor Antagonist Psi-conotoxin PIIIF'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1JLP OCA].

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==

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: Ireland, C.M.]]

[[Category: Ireland, C M.]]

[[Category: Wagoner, R.M.Van.]]

[[Category: Wagoner, R M.Van.]]

[[Category: NH2]]

[[Category: amidated c-terminus]]

[[Category: multiple disulfide bonds]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Tue Nov 20 18~~:22:07 ~~2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:24:07 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:1jlp.gif|left|200px]]<br /><applet load="1jlp" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1jlp.gif|left|200px]]<br /><applet load="1jlp" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1jlp" />
 '''Solution Structure of the Noncompetitive Skeletal Muscle Nicotinic Acetylcholine Receptor Antagonist Psi-conotoxin PIIIF'''<br />
 ==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.
+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==
-JLP 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JLP OCA].
+JLP 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==
 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: Ireland, C.M.]]
+[[Category: Ireland, C M.]]
-[[Category: Wagoner, R.M.Van.]]
+[[Category: Wagoner, R M.Van.]]
 [[Category: NH2]]
 [[Category: amidated c-terminus]]
 [[Category: multiple disulfide bonds]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:22:07 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:24:07 2008''