2ak0
From Proteopedia
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. 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 Sat May 3 19:08:49 2008
