{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fan J"],"funding":["Chinese National Programs for Brain Science and Brain-like Intelligence Technology","Novartis Pharma AG","New Cornerstone Science Foundation","Beijing National Laboratory for Molecular Sciences","National Natural Science Foundation of China","National Key Research and Development Program of China","Ningxia Hui Autonomous Region Key Research and Development Project"],"pagination":["e2401583"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11220649"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(25)"],"pubmed_abstract":["The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo-electron microscopy (cryo-EM) structures of human TRPV4 are presented in-complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage-sensing-like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4"],"journal":["Advanced science (Weinheim, Baden-Wurttemberg, Germany)"],"pubmed_title":["Structural Pharmacology of TRPV4 Antagonists."],"pmcid":["PMC11220649"],"funding_grant_id":["2021ZD0202102","XPLORERPRIZE","22177006","BNLMS- CXX-202106","82271498","2022YFC2502500","BNLMS‐ CXX‐202106","22193073","BiocatalystDevelopmentGrant","92253305","2022BEG02042"],"pubmed_authors":["Ke H","Xie W","Lei J","Fan J","Huang Z","Lei X","Liao D","Guo C","Tang Y","Tominaga M"],"additional_accession":[]},"is_claimable":false,"name":"Structural Pharmacology of TRPV4 Antagonists.","description":"The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo-electron microscopy (cryo-EM) structures of human TRPV4 are presented in-complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage-sensing-like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-06-01T09:50:24.391Z","creation":"2025-04-04T12:21:47.716Z"},"accession":"S-EPMC11220649","cross_references":{"pubmed":["38659239"],"doi":["10.1002/advs.202401583"]}}