2025/03/29 by Gagan Sharma, Jennifer R. Deuis, Xinying Jia +6 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Biochemical and Structural Characterization #Ion channel regulation and function #Nicotinic Acetylcholine Receptors Study
paper · doi:10.1002/1873-3468.70036
openalex publication_date 2025/03/29 · openalex created_date 2025/03/31 · openalex updated_date 2026/06/22
Ion channels are among the main targets of venom peptides. Extensive functional screening has identified a number of these peptides as modulators of the voltage‐gated sodium channel subtype Na V 1.7, a potential target for the treatment of chronic pain. In this study, we used a bioinformatic approach that can automatically identify Na V 1.7 gating modifier toxins from sequence information alone. The method further enables the incorporation of evolutionarily accessible sequence space in structure–activity relationship studies. The in silico method identified a putative Na V 1.7 inhibitor, μ‐theraphotoxin Cg4a, which we produced recombinantly and confirmed as a Na V 1.7 inhibitor. Using structural and mutagenesis studies, we propose an improved definition of the pharmacophore of this class of Na V 1.7 inhibitors, aiding future in silico screening and classification of Na V 1.7 inhibitors.