2ak0
From Proteopedia
(New page: 200px<br /><applet load="2ak0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ak0" /> '''Structure of cyclic conotoxin MII-7'''<br />...) |
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'''Structure of cyclic conotoxin MII-7'''<br /> | '''Structure of cyclic conotoxin MII-7'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Conotoxins (CTXs), with their exquisite specificity and potency, have | + | Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, their beneficial activities may potentially be undermined by susceptibility to proteolysis in vivo. By cyclizing the alpha-CTX MII by using a range of linkers, we have engineered peptides that preserve their full activity but have greatly improved resistance to proteolytic degradation. The cyclic MII analogue containing a seven-residue linker joining the N and C termini was as active and selective as the native peptide for native and recombinant neuronal nicotinic acetylcholine receptor subtypes present in bovine chromaffin cells and expressed in Xenopus oocytes, respectively. Furthermore, its resistance to proteolysis against a specific protease and in human plasma was significantly improved. More generally, to our knowledge, this report is the first on the cyclization of disulfide-rich toxins. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine. |
==About this Structure== | ==About this Structure== | ||
| - | 2AK0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 2AK0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AK0 OCA]. |
==Reference== | ==Reference== | ||
Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII., Clark RJ, Fischer H, Dempster L, Daly NL, Rosengren KJ, Nevin ST, Meunier FA, Adams DJ, Craik DJ, Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13767-72. Epub 2005 Sep 14. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16162671 16162671] | Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII., Clark RJ, Fischer H, Dempster L, Daly NL, Rosengren KJ, Nevin ST, Meunier FA, Adams DJ, Craik DJ, Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13767-72. Epub 2005 Sep 14. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16162671 16162671] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Adams, D | + | [[Category: Adams, D J.]] |
| - | [[Category: Clark, R | + | [[Category: Clark, R J.]] |
| - | [[Category: Craik, D | + | [[Category: Craik, D J.]] |
| - | [[Category: Daly, N | + | [[Category: Daly, N L.]] |
[[Category: Dempster, L.]] | [[Category: Dempster, L.]] | ||
[[Category: Fischer, H.]] | [[Category: Fischer, H.]] | ||
| - | [[Category: Meunier, F | + | [[Category: Meunier, F A.]] |
| - | [[Category: Nevin, S | + | [[Category: Nevin, S T.]] |
| - | [[Category: Rosengren, K | + | [[Category: Rosengren, K J.]] |
[[Category: alpha-helix]] | [[Category: alpha-helix]] | ||
[[Category: cyclic backbone]] | [[Category: cyclic backbone]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:28:11 2008'' |
Revision as of 14:28, 21 February 2008
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Structure of cyclic conotoxin MII-7
Overview
Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, their beneficial activities may potentially be undermined by susceptibility to proteolysis in vivo. By cyclizing the alpha-CTX MII by using a range of linkers, we have engineered peptides that preserve their full activity but have greatly improved resistance to proteolytic degradation. The cyclic MII analogue containing a seven-residue linker joining the N and C termini was as active and selective as the native peptide for native and recombinant neuronal nicotinic acetylcholine receptor subtypes present in bovine chromaffin cells and expressed in Xenopus oocytes, respectively. Furthermore, its resistance to proteolysis against a specific protease and in human plasma was significantly improved. More generally, to our knowledge, this report is the first on the cyclization of disulfide-rich toxins. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine.
About this Structure
2AK0 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII., Clark RJ, Fischer H, Dempster L, Daly NL, Rosengren KJ, Nevin ST, Meunier FA, Adams DJ, Craik DJ, Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13767-72. Epub 2005 Sep 14. PMID:16162671
Page seeded by OCA on Thu Feb 21 16:28:11 2008
