| Structural highlights
Function
NTA_PSARE Gating-modifier toxin that both inhibits the peak current of human Nav1.1/SCN1A, rat Nav1.2/SCN2A, human Nav1.6/SCN8A, and human Nav1.7/SCN9A and concurrently inhibits fast inactivation of human Nav1.1 and rat Nav1.3/SCN3A. The relative rank order potency for Nav modulation is Nav1.3 (inactivation EC(50)=45 nM) > Nav1.7 > Nav1.2 > Nav1.1 (inactivation) > Nav1.1 > Nav1.6 > Nav1.3 (IC(50)=8 uM). The DII and DIV S3-S4 loops of Nav channel voltage sensors are important for the interaction of this toxin with Nav channels but cannot account for its unique subtype selectivity. It is the variability of the S1-S2 loops between NaV channels which contributes substantially to the selectivity profile observed for this toxin, particularly with regards to fast inactivation. This toxin may bind the channel in the resting state (Probable).[1] [2]
References
- ↑ Wingerd JS, Mozar CA, Ussing CA, Murali SS, Chin YK, Cristofori-Armstrong B, Durek T, Gilchrist J, Vaughan CW, Bosmans F, Adams DJ, Lewis RJ, Alewood PF, Mobli M, Christie MJ, Rash LD. The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity. Sci Rep. 2017 Apr 20;7(1):974. PMID:28428547 doi:10.1038/s41598-017-01129-0
- ↑ Wingerd JS, Mozar CA, Ussing CA, Murali SS, Chin YK, Cristofori-Armstrong B, Durek T, Gilchrist J, Vaughan CW, Bosmans F, Adams DJ, Lewis RJ, Alewood PF, Mobli M, Christie MJ, Rash LD. The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity. Sci Rep. 2017 Apr 20;7(1):974. PMID:28428547 doi:10.1038/s41598-017-01129-0
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