1npi
From Proteopedia
Tityus Serrulatus Neurotoxin (Ts1) at atomic resolution
Structural highlights
FunctionSCX1_TITSE Beta toxins bind voltage-independently at site-4 of sodium channels (Nav) and shift the voltage of activation toward more negative potentials thereby affecting sodium channel activation and promoting spontaneous and repetitive firing. In addition, it stimulates the release of NO, IL-6 and TNF-alpha in J774.1 cells (PubMed:21549737). This toxin is active against both mammals and insects.[1] Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe structure of the Ts1 toxin from the Brazilian scorpion Tityus serrulatus was investigated at atomic resolution using X-ray crystallography. Several positively charged niches exist on the Ts1 molecular surface, two of which were found to coordinate phosphate ions present in the crystallization solution. One phosphate ion is bound to the conserved basic Lys1 residue at the Ts1 N-terminus and to residue Asn49. The second ion was found to be caged by residues Lys12, Trp54 and Arg56. Lys12 and Tyr/Trp54 residues are strictly conserved in all classical scorpion beta-neurotoxins. The cavity formed by these residues may represent a special scaffold required for interaction between beta-neurotoxins and sodium channels. The charge distribution on the Ts1 surface and the results of earlier chemical modification studies and side-directed mutagenesis experiments strongly indicate that the phosphate-ion positions mark plausible binding sites to the Na(+) channel. The existence of two distinct binding sites on the Ts1 molecular surface provides an explanation for the competition between Ts1, depressant (LqhIT2) and excitatory (AaHIT) neurotoxins. Structural analysis of Tityus serrulatus Ts1 neurotoxin at atomic resolution: insights into interactions with Na+ channels.,Pinheiro CB, Marangoni S, Toyama MH, Polikarpov I Acta Crystallogr D Biol Crystallogr. 2003 Mar;59(Pt 3):405-15. Epub 2003, Feb 21. PMID:12595696[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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