2KIR

Solution structure of a designer toxin, mokatoxin-1

2KIR の概要

• エントリーDOI: 10.2210/pdb2kir/pdb
• 分子名称: Designer toxin (1 entity in total)
• 機能のキーワード: venom, scorpion, phage display, toxin, mokatoxin, moka1
• 由来する生物種: synthetic
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3890.80

構造登録者

Biancalana, M.,Koide, A.,Takacs, Z.,Goldstein, S.,Koide, S. (登録日: 2009-05-07, 公開日: 2009-12-29, 最終更新日: 2024-10-09)

主引用文献

Takacs, Z.,Toups, M.,Kollewe, A.,Johnson, E.,Cuello, L.G.,Driessens, G.,Biancalana, M.,Koide, A.,Ponte, C.G.,Perozo, E.,Gajewski, T.F.,Suarez-Kurtz, G.,Koide, S.,Goldstein, S.A.
A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library.
Proc.Natl.Acad.Sci.USA, 106:22211-22216, 2009

PubMed Abstract: Venomous animals immobilize prey using protein toxins that act on ion channels and other targets of biological importance. Broad use of toxins for biomedical research, diagnosis, and therapy has been limited by inadequate target discrimination, for example, among ion channel subtypes. Here, a synthetic toxin is produced by a new strategy to be specific for human Kv1.3 channels, critical regulators of immune T cells. A phage display library of 11,200 de novo proteins is designed using the alpha-KTx scaffold of 31 scorpion toxin sequences known or predicted to bind to potassium channels. Mokatoxin-1 (moka1) is isolated by affinity selection on purified target. Moka1 blocks Kv1.3 at nanomolar levels that do not inhibit Kv1.1, Kv1.2, or KCa1.1. As a result, moka1 suppresses CD3/28-induced cytokine secretion by T cells without cross-reactive gastrointestinal hyperactivity. The 3D structure of moka1 rationalizes its specificity and validates the engineering approach, revealing a unique interaction surface supported on an alpha-KTx scaffold. This scaffold-based/target-biased strategy overcomes many obstacles to production of selective toxins.

PubMed: 20007782
DOI: 10.1073/pnas.0910123106

実験手法

SOLUTION NMR