Structural highlights
Function
SCX3_TITSE Binds voltage-dependently at site-3 of sodium channels (Nav) and inhibits the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals (mice).[1] [2] [3]
Publication Abstract from PubMed
Ts3 is an alpha scorpion toxin from the venom of the Brazilian scorpion Tityus serrulatus. Ts3 binds to the domain IV voltage sensor of voltage-gated sodium channels (Nav ) and slows down their fast inactivation. The covalent structure of the Ts3 toxin is uncertain, and the structure of the folded protein molecule is unknown. Herein, we report the total chemical synthesis of four candidate Ts3 toxin protein molecules and the results of structure-activity studies that enabled us to establish the covalent structure of biologically active Ts3 toxin. We also report the synthesis of the mirror image form of the Ts3 protein molecule, and the use of racemic protein crystallography to determine the folded (tertiary) structure of biologically active Ts3 toxin by X-ray diffraction.
Elucidation of the Covalent and Tertiary Structures of Biologically Active Ts3 Toxin.,Dang B, Kubota T, Mandal K, Correa AM, Bezanilla F, Kent SB Angew Chem Int Ed Engl. 2016 May 31. doi: 10.1002/anie.201603420. PMID:27244051[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Campos FV, Moreira TH, Beirao PS, Cruz JS. Veratridine modifies the TTX-resistant Na+ channels in rat vagal afferent neurons. Toxicon. 2004 Mar 15;43(4):401-6. PMID:15051403 doi:http://dx.doi.org/10.1016/j.toxicon.2004.01.012
- ↑ Campos FV, Coronas FI, Beirao PS. Voltage-dependent displacement of the scorpion toxin Ts3 from sodium channels and its implication on the control of inactivation. Br J Pharmacol. 2004 Aug;142(7):1115-22. Epub 2004 Jul 12. PMID:15249424 doi:http://dx.doi.org/10.1038/sj.bjp.0705793
- ↑ Kirsch GE, Skattebol A, Possani LD, Brown AM. Modification of Na channel gating by an alpha scorpion toxin from Tityus serrulatus. J Gen Physiol. 1989 Jan;93(1):67-83. PMID:2536799
- ↑ Dang B, Kubota T, Mandal K, Correa AM, Bezanilla F, Kent SB. Elucidation of the Covalent and Tertiary Structures of Biologically Active Ts3 Toxin. Angew Chem Int Ed Engl. 2016 May 31. doi: 10.1002/anie.201603420. PMID:27244051 doi:http://dx.doi.org/10.1002/anie.201603420
