5O0U

Crystal structure of tarantula venom peptide Protoxin-II

5O0U の概要

• エントリーDOI: 10.2210/pdb5o0u/pdb
• 分子名称: Beta/omega-theraphotoxin-Tp2a, CHLORIDE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: inhibitor cystine knot, ion channel inhibitors, venom, toxin
• 由来する生物種: Thrixopelma pruriens (green velvet)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4034.73

構造登録者

Tabor, A.,McCarthy, S.,Reyes, F.E. (登録日: 2017-05-17, 公開日: 2017-09-13, 最終更新日: 2024-10-16)

主引用文献

Wright, Z.V.F.,McCarthy, S.,Dickman, R.,Reyes, F.E.,Sanchez-Martinez, S.,Cryar, A.,Kilford, I.,Hall, A.,Takle, A.K.,Topf, M.,Gonen, T.,Thalassinos, K.,Tabor, A.B.
The Role of Disulfide Bond Replacements in Analogues of the Tarantula Toxin ProTx-II and Their Effects on Inhibition of the Voltage-Gated Sodium Ion Channel Nav1.7.
J.Am.Chem.Soc., 139:13063-13075, 2017

PubMed Abstract: Spider venom toxins, such as Protoxin-II (ProTx-II), have recently received much attention as selective Na1.7 channel blockers, with potential to be developed as leads for the treatment of chronic nocioceptive pain. ProTx-II is a 30-amino acid peptide with three disulfide bonds that has been reported to adopt a well-defined inhibitory cystine knot (ICK) scaffold structure. Potential drawbacks with such peptides include poor pharmacodynamics and potential scrambling of the disulfide bonds in vivo. In order to address these issues, in the present study we report the solid-phase synthesis of lanthionine-bridged analogues of ProTx-II, in which one of the three disulfide bridges is replaced with a thioether linkage, and evaluate the biological properties of these analogues. We have also investigated the folding and disulfide bridging patterns arising from different methods of oxidation of the linear peptide precursor. Finally, we report the X-ray crystal structure of ProTx-II to atomic resolution; to our knowledge this is the first crystal structure of an ICK spider venom peptide not bound to a substrate.

PubMed: 28880078
DOI: 10.1021/jacs.7b06506

実験手法

X-RAY DIFFRACTION (0.99 Å)