C-Terminal residues in small potassium channel blockers OdK1 and OSK3 from scorpion venom fine-tune the selectivity

被引：6

作者：

Kuzmenkov, Alexey I. ^{[1
,2
]}

Peigneur, Steve ^{[3
]}

Chugunov, Anton O. ^{[1
,4
]}

Tabakmakher, Valentin M. ^{[1
]}

Efremov, Roman G. ^{[1
,4
]}

Tytgat, Jan ^{[3
]}

Grishin, Eugene V. ^{[1
]}

Vassilevski, Alexander A. ^{[1
,2
]}

机构：

[1] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia

[2] Lomonosov Moscow State Univ, Biol Fac, Moscow 119992, Russia

[3] Univ Leuven, Toxicol & Pharmacol, B-3000 Louvain, Belgium

[4] Natl Res Univ, Higher Sch Econ, Moscow 101000, Russia

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2017年 / 1865卷 / 05期

基金：

俄罗斯科学基金会;

关键词：

Scorpion toxins; Voltage-gated potassium channels; Pore blockers; Cysteine-stabilized alpha/beta fold (CS alpha/beta); KTx; KV1.3; CHANNEL; THERAPEUTIC TARGET; K+ CHANNELS; TOXIN; PEPTIDE; PURIFICATION; SPECIFICITY; SIMULATIONS; INHIBITOR; PROTEIN;

D O I：

10.1016/j.bbapap.2017.02.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report isolation, sequencing, and electrophysiological characterization of OSK3 (alpha-KTx 8.8 in Kalium and Uniprot databases), a potassium channel blocker from the scorpion Orthochirus scrobiculosus venom. Using the voltage clamp technique, OSK3 was tested on a wide panel of 11 voltage-gated potassium channels expressed in Xenopus oocytes, and was found to potently inhibit Kv1.2 and Kv1.3 with IC50 values of similar to 331 nM and similar to 503 nM, respectively. OdK1 produced by the scorpion Odontobuthus doriae differs by just two C-terminal residues from OSK3, but shows marked preference to Kv1.2. Based on the charybdotoxin-potassium channel complex crystal structure, a model was built to explain the role of the variable residues in OdK1 and OSK3 selectivity. (C) 2017 Elsevier B.V. All rights reserved.

引用

页码：465 / 472

页数：8