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1NIY

THREE DIMENSIONAL SOLUTION STRUCTURE OF HAINANTOXIN-IV BY 2D 1H-NMR

1NIY の概要
エントリーDOI10.2210/pdb1niy/pdb
NMR情報BMRB: 5674
分子名称HAINANTOXIN-IV (1 entity in total)
機能のキーワードneurotoxin, inhibitor cystine knot motif, toxin
由来する生物種Ornithoctonus hainana
タンパク質・核酸の鎖数1
化学式量合計3999.63
構造登録者
Li, D.,Lu, S.,Gu, X.,Liang, S. (登録日: 2002-12-30, 公開日: 2003-01-14, 最終更新日: 2024-10-30)
主引用文献Li, D.,Xiao, Y.,Xu, X.,Xiong, X.,Lu, S.,Liu, Z.,Zhu, Q.,Wang, M.,Gu, X.,Liang, S.
Structure-Activity Relationships of Hainantoxin-IV and Structure Determination of Active and Inactive Sodium Channel Blockers.
J.Biol.Chem., 279:37734-37740, 2004
Cited by
PubMed Abstract: Hainantoxin-IV (HNTX-IV) can specifically inhibit the neuronal tetrodotoxin-sensitive sodium channels and defines a new class of depressant spider toxin. The sequence of native HNTX-IV is ECLGFGKGCNPSNDQCCKSSNLVCSRKHRWCKYEI-NH(2). In the present study, to obtain further insight into the primary and tertiary structural requirements of neuronal sodium channel blockers, we determined the solution structure of HNTX-IV as a typical inhibitor cystine knot motif and synthesized four mutants designed based on the predicted sites followed by structural elucidation of two inactive mutants. Pharmacological studies indicated that the S12A and R26A mutants had activities near that of native HNTX-IV, while K27A and R29A demonstrated activities reduced by 2 orders of magnitude. (1)H MR analysis showed the similar molecular conformations for native HNTX-IV and four synthetic mutants. Furthermore, in the determined structures of K27A and R29A, the side chains of residues 27 and 29 were located in the identical spatial position to those of native HNTX-IV. These results suggested that residues Ser(12), Arg(26), Lys(27), and Arg(29) were not responsible for stabilizing the distinct conformation of HNTX-IV, but Lys(27) and Arg(29) were critical for the bioactivities. The potency reductions produced by Ala substitutions were primarily due to the direct interaction of the essential residues Lys(27) and Arg(29) with sodium channels rather than to a conformational change. After comparison of these structures and activities with correlated toxins, we hypothesized that residues Lys(27), Arg(29), His(28), Lys(32), Phe(5), and Trp(30) clustered on one face of HNTX-IV were responsible for ligand binding.
PubMed: 15201273
DOI: 10.1074/jbc.M405765200
主引用文献が同じPDBエントリー
実験手法
SOLUTION NMR
構造検証レポート
Validation report summary of 1niy
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件を2024-10-30に公開中

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