1cnn: Difference between revisions

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

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

caption="1cnn" />

'''OMEGA-CONOTOXIN MVIIC FROM CONUS MAGUS'''<br />

==Overview==

The omega-conotoxins are a set of structurally related, four-loop, six, cysteine containing peptides, that have a range of selectivities for, different subtypes of the voltage-sensitive calcium channel (VSCC). To, investigate the basis of the selectivity displayed by these peptides, we, have studied the binding affinities of two naturally occurring, omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop, hybrids using radioligand binding assays for N and P/Q-type Ca2+channels, in rat brain tissue. A selectivity profile was developed from the ratio of, relative potencies at N-type VSCCs (using [125I]GVIA radioligand binding, assays) and P/Q-type VSCCs (using [125I]MVIIC radioligand binding assays)., In these peptides, loops 2 and 4 make the greatest contribution to VSCC, subtype selectivity, while the effects of loops 1 and 3 are negligible., Peptides with homogenous combinations of loop 2 and 4 display clear, selectivity preferences, while those with heterogeneous combinations of, loops 2 and 4 are less discriminatory. 1H NMR spectroscopy revealed that, the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were, similar; however, several differences in local structure were identified., Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin, residues most likely to interact with the N-type VSCC.

The omega-conotoxins are a set of structurally related, four-loop, six cysteine containing peptides, that have a range of selectivities for different subtypes of the voltage-sensitive calcium channel (VSCC). To investigate the basis of the selectivity displayed by these peptides, we have studied the binding affinities of two naturally occurring omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop hybrids using radioligand binding assays for N and P/Q-type Ca2+channels in rat brain tissue. A selectivity profile was developed from the ratio of relative potencies at N-type VSCCs (using [125I]GVIA radioligand binding assays) and P/Q-type VSCCs (using [125I]MVIIC radioligand binding assays). In these peptides, loops 2 and 4 make the greatest contribution to VSCC subtype selectivity, while the effects of loops 1 and 3 are negligible. Peptides with homogenous combinations of loop 2 and 4 display clear selectivity preferences, while those with heterogeneous combinations of loops 2 and 4 are less discriminatory. 1H NMR spectroscopy revealed that the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were similar; however, several differences in local structure were identified. Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin residues most likely to interact with the N-type VSCC.

==About this Structure==

1CNN 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=1CNN OCA].

1CNN 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=1CNN OCA].

==Reference==

Line 13:

[[Category: Single protein]]

[[Category: Adams, D.]]

[[Category: Alewood, P.F.]]

[[Category: Alewood, P F.]]

[[Category: Bond, T.]]

[[Category: Craik, D.J.]]

[[Category: Craik, D J.]]

[[Category: Lewis, R.J.]]

[[Category: Lewis, R J.]]

[[Category: Nielsen, K.J.]]

[[Category: Nielsen, K J.]]

[[Category: Thomas, L.]]

[[Category: NH2]]

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[[Category: voltage-sensitive calcium channel antagonist]]

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@@ Line 1: / Line 1: @@
-[[Image:1cnn.gif|left|200px]]<br /><applet load="1cnn" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1cnn.gif|left|200px]]<br /><applet load="1cnn" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1cnn" />
 '''OMEGA-CONOTOXIN MVIIC FROM CONUS MAGUS'''<br />
 ==Overview==
-The omega-conotoxins are a set of structurally related, four-loop, six, cysteine containing peptides, that have a range of selectivities for, different subtypes of the voltage-sensitive calcium channel (VSCC). To, investigate the basis of the selectivity displayed by these peptides, we, have studied the binding affinities of two naturally occurring, omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop, hybrids using radioligand binding assays for N and P/Q-type Ca2+channels, in rat brain tissue. A selectivity profile was developed from the ratio of, relative potencies at N-type VSCCs (using [125I]GVIA radioligand binding, assays) and P/Q-type VSCCs (using [125I]MVIIC radioligand binding assays)., In these peptides, loops 2 and 4 make the greatest contribution to VSCC, subtype selectivity, while the effects of loops 1 and 3 are negligible., Peptides with homogenous combinations of loop 2 and 4 display clear, selectivity preferences, while those with heterogeneous combinations of, loops 2 and 4 are less discriminatory. 1H NMR spectroscopy revealed that, the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were, similar; however, several differences in local structure were identified., Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin, residues most likely to interact with the N-type VSCC.
+The omega-conotoxins are a set of structurally related, four-loop, six cysteine containing peptides, that have a range of selectivities for different subtypes of the voltage-sensitive calcium channel (VSCC). To investigate the basis of the selectivity displayed by these peptides, we have studied the binding affinities of two naturally occurring omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop hybrids using radioligand binding assays for N and P/Q-type Ca2+channels in rat brain tissue. A selectivity profile was developed from the ratio of relative potencies at N-type VSCCs (using [125I]GVIA radioligand binding assays) and P/Q-type VSCCs (using [125I]MVIIC radioligand binding assays). In these peptides, loops 2 and 4 make the greatest contribution to VSCC subtype selectivity, while the effects of loops 1 and 3 are negligible. Peptides with homogenous combinations of loop 2 and 4 display clear selectivity preferences, while those with heterogeneous combinations of loops 2 and 4 are less discriminatory. 1H NMR spectroscopy revealed that the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were similar; however, several differences in local structure were identified. Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin residues most likely to interact with the N-type VSCC.
 ==About this Structure==
-CNN 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=1CNN OCA].
+CNN 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=1CNN OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Single protein]]
 [[Category: Adams, D.]]
-[[Category: Alewood, P.F.]]
+[[Category: Alewood, P F.]]
 [[Category: Bond, T.]]
-[[Category: Craik, D.J.]]
+[[Category: Craik, D J.]]
-[[Category: Lewis, R.J.]]
+[[Category: Lewis, R J.]]
-[[Category: Nielsen, K.J.]]
+[[Category: Nielsen, K J.]]
 [[Category: Thomas, L.]]
 [[Category: NH2]]
@@ Line 23: / Line 23: @@
 [[Category: voltage-sensitive calcium channel antagonist]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:36:14 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:07:49 2008''