Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Revealing the Function and the Structural Model of Ts4: Insights into the ``Non-Toxic{''} Toxin from Tityus serrulatus Venom

Full text
Author(s):
Pucca, Manuela B. [1] ; Cerni, Felipe A. [1] ; Peigneur, Steve [2] ; Bordon, Karla C. F. [1] ; Tytgat, Jan [2] ; Arantes, Eliane C. [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Leuven, Toxicol & Pharmacol, B-3000 Leuven - Belgium
Total Affiliations: 2
Document type: Journal article
Source: TOXINS; v. 7, n. 7, p. 2534-2550, JUL 2015.
Web of Science Citations: 16
Abstract

The toxin, previously described as a non-toxic toxin, was isolated from the scorpion venom of Tityus serrulatus (Ts), responsible for the most severe and the highest number of accidents in Brazil. In this study, the subtype specificity and selectivity of Ts4 was investigated using six mammalian Nav channels (Nav1.2Nav1.6 and Nav1.8) and two insect Nav channels (DmNav1 and BgNav). The electrophysiological assays showed that Ts4 specifically inhibited the fast inactivation of Nav1.6 channels, the most abundant sodium channel expressed in the adult central nervous system, and can no longer be classified as a non-toxic peptide. Based on the results, we could classify the Ts4 as a classical -toxin. The Ts4 3D-structural model was built based on the solved X-ray Ts1 3D-structure, the major toxin from Ts venom with which it shares high sequence identity (65.57%). The Ts4 model revealed a flattened triangular shape constituted by three-stranded antiparallel -sheet and one -helix stabilized by four disulfide bonds. The absence of a Lys in the first amino acid residue of the N-terminal of Ts4 is probably the main responsible for its low toxicity. Other key amino acid residues important to the toxicity of - and -toxins are discussed here. (AU)

FAPESP's process: 13/21329-0 - Electrophysiological characterization of Tityus serrulatus venom toxins Ts3, Ts4, Ts6, Ts8, Ts15 and TS venom peptide 7: looking for new desired drugs
Grantee:Manuela Berto Pucca
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 13/21342-7 - Electrophysiological characterization of Ts19 fragment II, a new toxin purified from Tityus serrulatus venom
Grantee:Felipe Augusto Cerni
Support type: Scholarships abroad - Research Internship - Doctorate