2J15

Cyclic MrIA: An exceptionally stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter.

2J15 の概要

• エントリーDOI: 10.2210/pdb2j15/pdb
• NMR情報: BMRB: 7341
• 分子名称: MAI126P (1 entity in total)
• 機能のキーワード: toxin
• 由来する生物種: CONUS MARMOREUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1542.83

構造登録者

Lovelace, E.S.,Armishaw, C.J.,Colgrave, M.L.,Walstrom, M.E.,Alewood, P.F.,Daly, N.L.,Craik, D.J. (登録日: 2006-08-09, 公開日: 2006-11-01, 最終更新日: 2025-04-09)

主引用文献

Lovelace, E.S.,Armishaw, C.J.,Colgrave, M.L.,Wahlstrom, M.E.,Alewood, P.F.,Daly, N.L.,Craik, D.J.
Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter.
J. Med. Chem., 49:6561-6568, 2006

PubMed Abstract: Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.

PubMed: 17064074
DOI: 10.1021/jm060299h

実験手法

SOLUTION NMR