{"id":6548,"date":"2023-02-17T07:14:28","date_gmt":"2023-02-17T07:14:28","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2021-small-molecule-modulation-of-the-drosophila-slo-channel-elucidated-by-cryo-em\/"},"modified":"2023-02-17T07:14:29","modified_gmt":"2023-02-17T07:14:29","slug":"2021-small-molecule-modulation-of-the-drosophila-slo-channel-elucidated-by-cryo-em","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2021-small-molecule-modulation-of-the-drosophila-slo-channel-elucidated-by-cryo-em\/","title":{"rendered":"2021 &#8211; Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM"},"content":{"rendered":"<p>Slowpoke (Slo) potassium channels display extraordinarily high conductance, are synergistically activated by a positive transmembrane potential and high intracellular Ca<sup>2+<\/sup> concentrations and are important targets for insecticides and antiparasitic drugs. However, it is unknown how these compounds modulate ion translocation and whether there are insect-specific binding pockets. Here, we report structures of Drosophila Slo in the Ca<sup>2+<\/sup>-bound and Ca<sup>2+<\/sup>-free form and in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside. Whereas the architecture and gating mechanism of Slo channels are conserved, potential insect-specific binding pockets exist. Verruculogen inhibits K<sup>+<\/sup> transport by blocking the Ca<sup>2+<\/sup>-induced activation signal and precludes K<sup>+<\/sup> from entering the selectivity filter. Emodepside decreases the conductance by suboptimal K<sup>+<\/sup> coordination and uncouples ion gating from Ca<sup>2+<\/sup> and voltage sensing. Our results expand the mechanistic understanding of Slo regulation and lay the foundation for the rational design of regulators of Slo and other voltage-gated ion channels.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[61,335],"target_families":[354],"targets":[216],"resource_keyword":[],"class_list":["post-6548","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","target_categories-voltage-gated-ion-channels","target_categories-intracellular-regulated-ion-channels","target_families-calcium-and-sodium-activated-potassium-channels-kca-and-kna","targets-kca1-1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6548","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6548"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6548"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6548"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6548"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6548"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6548"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6548"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6548"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6548"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}