Structure-function and rational design of a spider toxin Ssp1a at human voltage-gated sodium channel subtypes.

ABSTRACT: The structure-function and optimization studies of Na_V-inhibiting spider toxins have focused on developing selective inhibitors for peripheral pain-sensing Na_V1.7. With several Na_V subtypes emerging as potential therapeutic targets, structure-function analysis of Na_V-inhibiting spider toxins at such subtypes is warranted. Using the recently discovered spider toxin Ssp1a, this study extends the structure-function relationships of Na_V-inhibiting spider toxins beyond Na_V1.7 to include the epilepsy target Na_V1.2 and the pain target Na_V1.3. Based on these results and docking studies, we designed analogues for improved potency and/or subtype-selectivity, with S7R-E18K-rSsp1a and N14D-P27R-rSsp1a identified as

SUBMITTER: Dongol Y 

PROVIDER: S-EPMC10682951 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature