{"id":17713,"date":"2025-07-11T13:43:49","date_gmt":"2025-07-11T13:43:49","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=17713"},"modified":"2025-07-11T13:43:49","modified_gmt":"2025-07-11T13:43:49","slug":"2025-high-throughput-cryo-em-provides-structural-understanding-for-modulators-of-the-lysosomal-ion-channel-trpml1","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2025-high-throughput-cryo-em-provides-structural-understanding-for-modulators-of-the-lysosomal-ion-channel-trpml1\/","title":{"rendered":"2025 &#8211; High throughput cryo-EM provides structural understanding for modulators of the lysosomal ion channel TRPML1"},"content":{"rendered":"<p>Access to high-resolution structural data for protein-ligand complexes is a prerequisite for structure-based medicinal chemistry, where the ability to iterate cycles of design-structure-redesign is highly desirable. For proteins refractory to X-ray crystallography, such as integral membrane proteins, enablement of high throughput structure determination by cryoelectron microscopy (cryo-EM) has the potential to be transformational for structure-based design. We have applied such an approach to the lysosomal ion channel transient receptor potential mucolipin 1 (TRPML1) in complex with ten chemically diverse modulators, both agonists and antagonists. The resulting depth of high-resolution structural data generated provides important insights into protein-ligand structure-function relationships, including mechanistic understanding of ligand-induced channel pore opening and closing. Moreover, the knowledge gained has the potential to support iterative design cycles toward improved modulators of this important biological target.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,53,76],"therapeutic_areas":[143,403],"target_categories":[338],"target_families":[339],"targets":[251],"resource_keyword":[],"class_list":["post-17713","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","application_areas-drug-discovery","therapeutic_areas-assay-development-and-validation","therapeutic_areas-lysosomal-diseases","target_categories-other-ion-channels","target_families-trp-channels","targets-trpml1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/17713","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=17713"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=17713"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=17713"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=17713"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=17713"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=17713"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=17713"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=17713"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=17713"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}