2Z3S

NMR structure of AgTx2-MTX

2Z3S の概要

• エントリーDOI: 10.2210/pdb2z3s/pdb
• NMR情報: BMRB: 15299
• 分子名称: AgTx2-MTX (1 entity in total)
• 機能のキーワード: toxin, inhibitory cystine knot, chimera, maurotoxin, agitoxin
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4107.85

構造登録者

Pimentel, C.,M'Barrek, S.,Visan, V.,Grissmer, S.,Sabatier, J.M.,Darbon, H.,Fajloun, Z. (登録日: 2007-06-06, 公開日: 2008-04-22, 最終更新日: 2024-10-30)

主引用文献

Pimentel, C.,M'Barek, S.,Visan, V.,Grissmer, S.,Sampieri, F.,Sabatier, J.M.,Darbon, H.,Fajloun, Z.
Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX chimera, a new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion toxins.
Protein Sci., 17:107-118, 2008

PubMed Abstract: Agitoxin 2 (AgTx2) is a 38-residue scorpion toxin, cross-linked by three disulfide bridges, which acts on voltage-gated K(+) (Kv) channels. Maurotoxin (MTX) is a 34-residue scorpion toxin with an uncommon four-disulfide bridge reticulation, acting on both Ca(2+)-activated and Kv channels. A 39-mer chimeric peptide, named AgTx2-MTX, was designed from the sequence of the two toxins and chemically synthesized. It encompasses residues 1-5 of AgTx2, followed by the complete sequence of MTX. As established by enzyme cleavage, the new AgTx2-MTX molecule displays half-cystine pairings of the type C1-C5, C2-C6, C3-C7, and C4-C8, which is different from that of MTX. The 3D structure of AgTx2-MTX solved by (1)H-NMR, revealed both alpha-helical and beta-sheet structures, consistent with a common alpha/beta scaffold of scorpion toxins. Pharmacological assays of AgTx2-MTX revealed that this new molecule is more potent than both original toxins in blocking rat Kv1.2 channel. Docking simulations, performed with the 3D structure of AgTx2-MTX, confirmed this result and demonstrated the participation of the N-terminal domain of AgTx2 in its increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicated that replacement of the N-terminal domain of MTX by the one of AgTx2 in the AgTx2-MTX chimera results in a reorganization of the disulfide bridge arrangement and an increase of affinity to the Kv1.2 channel.

PubMed: 18042681
DOI: 10.1110/ps.073122908

実験手法

SOLUTION NMR