1G2G

MINIMAL CONFORMATION OF THE ALPHA-CONOTOXIN IMI FOR THE ALPHA7 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR RECOGNITION

1G2G の概要

• エントリーDOI: 10.2210/pdb1g2g/pdb
• 分子名称: ALPHA-CONOTOXIN IMI (1 entity in total)
• 機能のキーワード: alpha-helix, 3-10 helix, toxin
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1356.60

構造登録者

Lamthanh, H.,Jegou-Matheron, C.,Servent, D.,Menez, A.,Lancelin, J.M. (登録日: 2000-10-19, 公開日: 2000-11-08, 最終更新日: 2024-10-30)

主引用文献

Lamthanh, H.,Jegou-Matheron, C.,Servent, D.,Menez, A.,Lancelin, J.M.
Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies.
FEBS Lett., 454:293-298, 1999

PubMed Abstract: The alpha-ImI conotoxin, a selective potent inhibitor of the mammalian neuronal alpha7 nicotinic acetylcholine receptor (n-AchR), was shown by point mutation or by L-alanine scanning to display two regions essential for bioactivity: the active site Asp5-Pro6-Arg7 in the first loop and Trp10 in the second loop. The deletion of the Cys3,Cys12 disulfide bond in the alpha-ImI scaffold, e.g. peptide II, had no effect on its binding affinity. CD spectra, NMR studies and structure calculations were carried out on the wild type alpha-ImI, the weakest analog (R7A) and peptide II (equipotent to alpha-ImI) in order to point out the conformational differences between these compounds. Then, an attempt to correlate the conformational data and the affinity results was proposed. CD and NMR data were identical for the R7A analog and alpha-ImI, revealing the crucial functional role of the Arg7 side chain. On the other hand, the scaffold of the first loop in peptide II was shown by NMR to represent the minimal conformation for the optimal interaction of the toxin with the neuronal alpha7 n-AchR. Last, the beta-turn forming property of the 6th residue (Pro) in the active site of the alpha-ImI can be correlated with its affinity.

PubMed: 10431825
DOI: 10.1016/S0014-5793(99)00831-5

実験手法

SOLUTION NMR