1d7t: Difference between revisions

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[[Image:1d7t.gif|left|200px]]<br /><applet load="1d7t" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1d7t.gif|left|200px]]<br /><applet load="1d7t" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1d7t" />

'''NMR STRUCTURE OF AN ENGINEERED CONTRYPHAN CYCLIC PEPTIDE (MOTIF CPXXPXC)'''<br />

==Overview==

Contryphan-R, from venom of the cone-shell Conus radiatus, represents a, novel cyclic peptide scaffold onto which residues may be grafted to mimic, unrelated protein surfaces. Three substitutions were made at the x and X, positions of the disulfide-bridged motif CPxXPXC, where X and x represent, any L- and D-handed residues, respectively, P represents proline or, hydroxyproline, and C a half-cystine. These substitutions were designed to, mimic part of the pharmacophore of the unrelated globular polypeptide, omega-conotoxin GVIA, which blocks N-type calcium channels. The structure, of this engineered contryphan, YNK-contryphan-R ([D-Tyr4, Asn5, Lys7]contryphan-R), is shown to be similar to that of native contryphan-R, (Pallaghy et al., Biochemistry, 1999, Vol. 38, pp. 13553-13559), confirming that the scaffold is robust with respect to the multiple, substitutions. In particular, the alpha-beta bond vectors characterising, the orientation of the side chains relative to the backbone are similar in, contryphan-R, YNK-contryphan-R, and omega-conotoxin GVIA, which is the, required result for a scaffold-based approach to molecular design. The, solution structure of YNK-contryphan-R has an N-terminal, nonhydrogen-bonded, chain reversal centered on Hyp3-D-Trp4, and a, C-terminal type I beta-turn. A minor form due to cis-trans isomerism of, the Hyp2-Cys3 peptide bond is present in YNK-contryphan-R in a larger, proportion than in contryphan-R. It is evident, particularly from the, (3)J(HalphaHN) coupling constants, that YNK-contryphan-R is more flexible, than contryphan-R, probably due to the absence in YNK-contryphan-R of the, Pro-Trp packing present in the native molecule. Nevertheless, the, structure confirms that cyclic peptide molecular designs can achieve the, intended conformations.

Contryphan-R, from venom of the cone-shell Conus radiatus, represents a novel cyclic peptide scaffold onto which residues may be grafted to mimic unrelated protein surfaces. Three substitutions were made at the x and X positions of the disulfide-bridged motif CPxXPXC, where X and x represent any L- and D-handed residues, respectively, P represents proline or hydroxyproline, and C a half-cystine. These substitutions were designed to mimic part of the pharmacophore of the unrelated globular polypeptide omega-conotoxin GVIA, which blocks N-type calcium channels. The structure of this engineered contryphan, YNK-contryphan-R ([D-Tyr4, Asn5, Lys7]contryphan-R), is shown to be similar to that of native contryphan-R (Pallaghy et al., Biochemistry, 1999, Vol. 38, pp. 13553-13559), confirming that the scaffold is robust with respect to the multiple substitutions. In particular, the alpha-beta bond vectors characterising the orientation of the side chains relative to the backbone are similar in contryphan-R, YNK-contryphan-R, and omega-conotoxin GVIA, which is the required result for a scaffold-based approach to molecular design. The solution structure of YNK-contryphan-R has an N-terminal, nonhydrogen-bonded, chain reversal centered on Hyp3-D-Trp4, and a C-terminal type I beta-turn. A minor form due to cis-trans isomerism of the Hyp2-Cys3 peptide bond is present in YNK-contryphan-R in a larger proportion than in contryphan-R. It is evident, particularly from the (3)J(HalphaHN) coupling constants, that YNK-contryphan-R is more flexible than contryphan-R, probably due to the absence in YNK-contryphan-R of the Pro-Trp packing present in the native molecule. Nevertheless, the structure confirms that cyclic peptide molecular designs can achieve the intended conformations.

==About this Structure==

1D7T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1D7T OCA].

1D7T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D7T OCA].

==Reference==

The cyclic contryphan motif CPxXPXC, a robust scaffold potentially useful as an omega-conotoxin mimic., Pallaghy PK, Norton RS, Biopolymers. 2000 Sep;54(3):173-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10861378 10861378]

[[Category: Protein complex]]

[[Category: Norton, R.S.]]

[[Category: Norton, R S.]]

[[Category: Pallaghy, P.K.]]

[[Category: Pallaghy, P K.]]

[[Category: beta turn]]

[[Category: cis proline]]

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[[Category: disulfide bond]]

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@@ Line 1: / Line 1: @@
-[[Image:1d7t.gif|left|200px]]<br /><applet load="1d7t" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1d7t.gif|left|200px]]<br /><applet load="1d7t" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1d7t" />
 '''NMR STRUCTURE OF AN ENGINEERED CONTRYPHAN CYCLIC PEPTIDE (MOTIF CPXXPXC)'''<br />
 ==Overview==
-Contryphan-R, from venom of the cone-shell Conus radiatus, represents a, novel cyclic peptide scaffold onto which residues may be grafted to mimic, unrelated protein surfaces. Three substitutions were made at the x and X, positions of the disulfide-bridged motif CPxXPXC, where X and x represent, any L- and D-handed residues, respectively, P represents proline or, hydroxyproline, and C a half-cystine. These substitutions were designed to, mimic part of the pharmacophore of the unrelated globular polypeptide, omega-conotoxin GVIA, which blocks N-type calcium channels. The structure, of this engineered contryphan, YNK-contryphan-R ([D-Tyr4, Asn5, Lys7]contryphan-R), is shown to be similar to that of native contryphan-R, (Pallaghy et al., Biochemistry, 1999, Vol. 38, pp. 13553-13559), confirming that the scaffold is robust with respect to the multiple, substitutions. In particular, the alpha-beta bond vectors characterising, the orientation of the side chains relative to the backbone are similar in, contryphan-R, YNK-contryphan-R, and omega-conotoxin GVIA, which is the, required result for a scaffold-based approach to molecular design. The, solution structure of YNK-contryphan-R has an N-terminal, nonhydrogen-bonded, chain reversal centered on Hyp3-D-Trp4, and a, C-terminal type I beta-turn. A minor form due to cis-trans isomerism of, the Hyp2-Cys3 peptide bond is present in YNK-contryphan-R in a larger, proportion than in contryphan-R. It is evident, particularly from the, (3)J(HalphaHN) coupling constants, that YNK-contryphan-R is more flexible, than contryphan-R, probably due to the absence in YNK-contryphan-R of the, Pro-Trp packing present in the native molecule. Nevertheless, the, structure confirms that cyclic peptide molecular designs can achieve the, intended conformations.
+Contryphan-R, from venom of the cone-shell Conus radiatus, represents a novel cyclic peptide scaffold onto which residues may be grafted to mimic unrelated protein surfaces. Three substitutions were made at the x and X positions of the disulfide-bridged motif CPxXPXC, where X and x represent any L- and D-handed residues, respectively, P represents proline or hydroxyproline, and C a half-cystine. These substitutions were designed to mimic part of the pharmacophore of the unrelated globular polypeptide omega-conotoxin GVIA, which blocks N-type calcium channels. The structure of this engineered contryphan, YNK-contryphan-R ([D-Tyr4, Asn5, Lys7]contryphan-R), is shown to be similar to that of native contryphan-R (Pallaghy et al., Biochemistry, 1999, Vol. 38, pp. 13553-13559), confirming that the scaffold is robust with respect to the multiple substitutions. In particular, the alpha-beta bond vectors characterising the orientation of the side chains relative to the backbone are similar in contryphan-R, YNK-contryphan-R, and omega-conotoxin GVIA, which is the required result for a scaffold-based approach to molecular design. The solution structure of YNK-contryphan-R has an N-terminal, nonhydrogen-bonded, chain reversal centered on Hyp3-D-Trp4, and a C-terminal type I beta-turn. A minor form due to cis-trans isomerism of the Hyp2-Cys3 peptide bond is present in YNK-contryphan-R in a larger proportion than in contryphan-R. It is evident, particularly from the (3)J(HalphaHN) coupling constants, that YNK-contryphan-R is more flexible than contryphan-R, probably due to the absence in YNK-contryphan-R of the Pro-Trp packing present in the native molecule. Nevertheless, the structure confirms that cyclic peptide molecular designs can achieve the intended conformations.
 ==About this Structure==
-D7T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1D7T OCA].
+D7T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D7T OCA].
 ==Reference==
 The cyclic contryphan motif CPxXPXC, a robust scaffold potentially useful as an omega-conotoxin mimic., Pallaghy PK, Norton RS, Biopolymers. 2000 Sep;54(3):173-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10861378 10861378]
 [[Category: Protein complex]]
-[[Category: Norton, R.S.]]
+[[Category: Norton, R S.]]
-[[Category: Pallaghy, P.K.]]
+[[Category: Pallaghy, P K.]]
 [[Category: beta turn]]
 [[Category: cis proline]]
@@ Line 19: / Line 19: @@
 [[Category: disulfide bond]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:41:08 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:58 2008''