1d7t
From Proteopedia
(New page: 200px<br /><applet load="1d7t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d7t" /> '''NMR STRUCTURE OF AN ENGINEERED CONTRYPHAN CY...) |
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| - | [[Image:1d7t.gif|left|200px]]<br /><applet load="1d7t" size=" | + | [[Image:1d7t.gif|left|200px]]<br /><applet load="1d7t" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1d7t" /> | caption="1d7t" /> | ||
'''NMR STRUCTURE OF AN ENGINEERED CONTRYPHAN CYCLIC PEPTIDE (MOTIF CPXXPXC)'''<br /> | '''NMR STRUCTURE OF AN ENGINEERED CONTRYPHAN CYCLIC PEPTIDE (MOTIF CPXXPXC)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Contryphan-R, from venom of the cone-shell Conus radiatus, represents a | + | 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== | ==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:// | + | 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== | ==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] | 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: Protein complex]] | ||
| - | [[Category: Norton, R | + | [[Category: Norton, R S.]] |
| - | [[Category: Pallaghy, P | + | [[Category: Pallaghy, P K.]] |
[[Category: beta turn]] | [[Category: beta turn]] | ||
[[Category: cis proline]] | [[Category: cis proline]] | ||
| Line 19: | Line 19: | ||
[[Category: disulfide bond]] | [[Category: disulfide bond]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:58 2008'' |
Revision as of 10:13, 21 February 2008
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NMR STRUCTURE OF AN ENGINEERED CONTRYPHAN CYCLIC PEPTIDE (MOTIF CPXXPXC)
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.
About this Structure
1D7T is a Protein complex structure of sequences from [1]. Full crystallographic information is available from 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:10861378
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