2LU6

NMR solution structure of Midi peptide designed based on m-conotoxins

2LU6 の概要

• エントリーDOI: 10.2210/pdb2lu6/pdb
• NMR情報: BMRB: 18510
• 分子名称: Midi peptide designed based on m-conotoxins (1 entity in total)
• 機能のキーワード: m-conotoxin, kiiia, buiiic, de novo protein, toxin
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1700.95

構造登録者

Dyubankova, N.,Lescrinier, E.,Stevens, M.,Tytgat, J.,Herdewijn, P.,Peigneur, S. (登録日: 2012-06-08, 公開日: 2012-06-27, 最終更新日: 2024-11-06)

主引用文献

Stevens, M.,Peigneur, S.,Dyubankova, N.,Lescrinier, E.,Herdewijn, P.,Tytgat, J.
Design of bioactive peptides from naturally occurring mu-conotoxin structures.
J.Biol.Chem., 287:31382-31392, 2012

PubMed Abstract: To date, cone snail toxins ("conotoxins") are of great interest in the pursuit of novel subtype-selective modulators of voltage-gated sodium channels (Na(v)s). Na(v)s participate in a wide range of electrophysiological processes. Consequently, their malfunctioning has been associated with numerous diseases. The development of subtype-selective modulators of Na(v)s remains highly important in the treatment of such disorders. In current research, a series of novel, synthetic, and bioactive compounds were designed based on two naturally occurring μ-conotoxins that target Na(v)s. The initial designed peptide contains solely 13 amino acids and was therefore named "Mini peptide." It was derived from the μ-conotoxins KIIIA and BuIIIC. Based on this Mini peptide, 10 analogues were subsequently developed, comprising 12-16 amino acids with two disulfide bridges. Following appropriate folding and mass verification, blocking effects on Na(v)s were investigated. The most promising compound established an IC(50) of 34.1 ± 0.01 nM (R2-Midi on Na(v)1.2). An NMR structure of one of our most promising compounds was determined. Surprisingly, this structure does not reveal an α-helix. We prove that it is possible to design small peptides based on known pharmacophores of μ-conotoxins without losing their potency and selectivity. These data can provide crucial material for further development of conotoxin-based therapeutics.

PubMed: 22773842
DOI: 10.1074/jbc.M112.375733

実験手法

SOLUTION NMR