2AJW

Structure of the cyclic conotoxin MII-6

2AJW の概要

• エントリーDOI: 10.2210/pdb2ajw/pdb
• 関連するPDBエントリー: 2AK0
• NMR情報: BMRB: 6818
• 分子名称: Alpha-conotoxin MII (1 entity in total)
• 機能のキーワード: alpha-helix, cyclic backbone, toxin
• 細胞内の位置: Secreted: P56636
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2088.33

構造登録者

Clark, R.J.,Fischer, H.,Dempster, L.,Daly, N.L.,Rosengren, K.J.,Nevin, S.T.,Meunier, F.A.,Adams, D.J.,Craik, D.J. (登録日: 2005-08-02, 公開日: 2005-09-06, 最終更新日: 2024-11-13)

主引用文献

Clark, R.J.,Fischer, H.,Dempster, L.,Daly, N.L.,Rosengren, K.J.,Nevin, S.T.,Meunier, F.A.,Adams, D.J.,Craik, D.J.
Engineering stable peptide toxins by means of backbone cyclization: Stabilization of the {alpha}-conotoxin MII.
Proc.Natl.Acad.Sci.USA, 102:13767-13772, 2005

PubMed Abstract: 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.

PubMed: 16162671
DOI: 10.1073/pnas.0504613102
主引用文献が同じPDBエントリー

実験手法

SOLUTION NMR