7TVR

Structure of the ribbon isoform of the novel conotoxin PnID derived from Conus pennaceus

7TVR の概要

• エントリーDOI: 10.2210/pdb7tvr/pdb
• NMR情報: BMRB: 30992
• 分子名称: Chi-conotoxin-like PnMRCL-013 (1 entity in total)
• 機能のキーワード: venom peptide, toxin, conotoxin
• 由来する生物種: Conus pennaceus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1321.64

構造登録者

Loening, N.M.,Espiritu, M.J. (登録日: 2022-02-05, 公開日: 2023-01-25, 最終更新日: 2024-11-20)

主引用文献

Espiritu, M.J.,Taylor, J.K.,Sugai, C.K.,Thapa, P.,Loening, N.M.,Gusman, E.,Baoanan, Z.G.,Baumann, M.H.,Bingham, J.P.
Characterization of the Native Disulfide Isomers of the Novel chi-Conotoxin PnID: Implications for Further Increasing Conotoxin Diversity.
Mar Drugs, 21:-, 2023

PubMed Abstract: χ-Conotoxins are known for their ability to selectively inhibit norepinephrine transporters, an ability that makes them potential leads for treating various neurological disorders, including neuropathic pain. PnID, a peptide isolated from the venom of , shares high sequence homology with previously characterized χ-conotoxins. Whereas previously reported χ-conotoxins seem to only have a single native disulfide bonding pattern, PnID has three native isomers due to the formation of different disulfide bond patterns during its maturation in the venom duct. In this study, the disulfide connectivity and three-dimensional structure of these disulfide isomers were explored using regioselective synthesis, chromatographic coelution, and solution-state nuclear magnetic resonance spectroscopy. Of the native isomers, only the isomer with a ribbon disulfide configuration showed pharmacological activity similar to other χ-conotoxins. This isomer inhibited the rat norepinephrine transporter (IC = 10 ± 2 µM) and has the most structural similarity to previously characterized χ-conotoxins. In contrast, the globular isoform of PnID showed more than ten times less activity against this transporter and the beaded isoform did not display any measurable biological activity. This study is the first report of the pharmacological and structural characterization of an χ-conotoxin from a species other than and is the first report of the existence of natively-formed conotoxin isomers.

PubMed: 36827103
DOI: 10.3390/md21020061

実験手法

SOLUTION NMR