Solution structure of α-conotoxin MI determined by 1H-NMR spectroscopy and molecular dynamics simulation with the explicit solvent water

被引:34
作者
Gouda, H
Yamazaki, K
Hasegawa, J
Kobayashi, Y
Nishiuchi, Y
Sakakibara, S
Hirono, S
机构
[1] Kitasato Univ, Sch Pharmaceut Sci, Minato Ku, Tokyo 108, Japan
[2] Daiichi Pharmaceut Co Ltd, Inst Dev Res, Edogawa Ku, Tokyo 134, Japan
[3] Osaka Univ, Fac Pharmaceut Sci, Osaka 565, Japan
[4] Peptide Inst Inc, Prot Res Fdn, Osaka 562, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY | 1997年 / 1343卷 / 02期
关键词
solution structure; neurotoxin; 2D NMR; molecular dynamics simulation; acetylcholine receptor; (Conus magus);
D O I
10.1016/S0167-4838(97)00140-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The conformation of alpha-conotoxin MI, a potent antagonist of the nicotinic acetylcholine receptor, has been investigated in aqueous solution. Two-dimensional NMR experiments and simulated annealing calculations provide the overall topology of alpha-conotoxin MI; then molecular dynamics simulation with the explicit solvent water was followed in order to obtain a more reliable solution structure. The resulting conformation indicates the presence of a 3(I0) helix and a type I beta-turn for residues Pro6-Cys8 and Gly9-Try12, respectively, and shows a significant structural similarity to that of alpha-conotoxin GI, which has biological activity similar to that of MI. The present study provides a molecular basis for the alpha-conotoxin-receptor interaction. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:327 / 334
页数:8
相关论文
共 32 条
[31]   RELATIONSHIP BETWEEN THE BINDING-SITES FOR AN ALPHA-CONOTOXIN AND SNAKE-VENOM NEUROTOXINS IN THE NICOTINIC ACETYLCHOLINE-RECEPTOR FROM TORPEDO-CALIFORNICA [J].
UTKIN, YN ;
KOBAYASHI, Y ;
HUCHO, F ;
TSETLIN, VI .
TOXICON, 1994, 32 (09) :1153-1157
[32]   PHYLOGENETIC SPECIFICITY OF CHOLINERGIC LIGANDS - ALPHA-CONOTOXIN SI [J].
ZAFARALLA, GC ;
RAMILO, C ;
GRAY, WR ;
KARLSTROM, R ;
OLIVERA, BM ;
CRUZ, LJ .
BIOCHEMISTRY, 1988, 27 (18) :7102-7105