4LFS

High resolution x-ray structure of racemic ShK toxin

4LFS の概要

• エントリーDOI: 10.2210/pdb4lfs/pdb
• 関連するPDBエントリー: 4LFQ
• 分子名称: Potassium channel toxin ShK, CHLORIDE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: shk toxin, chemical protein synthesis, racemic protein crystallography, toxin
• 由来する生物種: Stichodactyla helianthus (Carribean sea anemone)
• 細胞内の位置: Secreted: P29187
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4303.80

構造登録者

Dang, B.,Kubota, T.,Mandal, K.,Bezanilla, F.,Kent, S.B.H. (登録日: 2013-06-27, 公開日: 2013-08-14, 最終更新日: 2024-11-20)

主引用文献

Dang, B.,Kubota, T.,Mandal, K.,Bezanilla, F.,Kent, S.B.
Native Chemical Ligation at Asx-Cys, Glx-Cys: Chemical Synthesis and High-Resolution X-ray Structure of ShK Toxin by Racemic Protein Crystallography.
J.Am.Chem.Soc., 135:11911-11919, 2013

PubMed Abstract: We have re-examined the utility of native chemical ligation at -Gln/Glu-Cys- [Glx-Cys] and -Asn/Asp-Cys- [Asx-Cys] sites. Using the improved thioaryl catalyst 4-mercaptophenylacetic acid (MPAA), native chemical ligation could be performed at -Gln-Cys- and Asn-Cys- sites without side reactions. After optimization, ligation at a -Glu-Cys- site could also be used as a ligation site, with minimal levels of byproduct formation. However, -Asp-Cys- is not appropriate for use as a site for native chemical ligation because of formation of significant amounts of β-linked byproduct. The feasibility of native chemical ligation at -Gln-Cys- enabled a convergent total chemical synthesis of the enantiomeric forms of the ShK toxin protein molecule. The D-ShK protein molecule was ~50,000-fold less active in blocking the Kv1.3 channel than the L-ShK protein molecule. Racemic protein crystallography was used to obtain high-resolution X-ray diffraction data for ShK toxin. The structure was solved by direct methods and showed significant differences from the previously reported NMR structures in some regions of the ShK protein molecule.

PubMed: 23919482
DOI: 10.1021/ja4046795

実験手法

X-RAY DIFFRACTION (0.97 Å)