
{"id":4136,"date":"2024-11-04T11:19:41","date_gmt":"2024-11-04T11:19:41","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/poster\/revisiting-the-serotonin-binding-pose-of-the-5-ht2a-receptor-with-cryo-em\/"},"modified":"2026-01-22T14:40:15","modified_gmt":"2026-01-22T14:40:15","slug":"revisiting-the-serotonin-binding-pose-of-the-5-ht2a-receptor-with-cryo-em","status":"publish","type":"poster","link":"https:\/\/www.sygnaturediscovery.com\/fr\/poster\/revisiting-the-serotonin-binding-pose-of-the-5-ht2a-receptor-with-cryo-em\/","title":{"rendered":"Revisiting the serotonin binding pose of the 5-HT2A receptor with cryo-EM"},"content":{"rendered":"<p>The 5-HT2A receptor is a central serotonin GPCR target in drug discovery, implicated in both psychiatric disorders and the pharmacology of psychedelic therapeutics. In this poster, Sygnature Discovery shares structural insights into serotonin&rsquo;s binding pose at 5-HT2A, obtained via cryo-electron microscopy (cryo-EM) &#8211; an approach that reveals novel confirmations missed by traditional crystallography.<\/p>\n<h3>Structural Biology Meets Drug Discovery<\/h3>\n<p>Cryo-EM has emerged as the preferred technique for elucidating GPCR structures, capturing both agonist-bound active states and, increasingly, antagonist-bound inactive states. However, obtaining these structures &#8211; especially inactive-state confirmations- can be challenging due to the size, flexibility and instability of GPCRs in isolation.<\/p>\n<p>This poster shared practical strategies and critical decision points for projects aimed at resolving GPCR complexes using cryo-EM. These insights are particularly relevant for teams pursuing structure-based drug design in the context of CNS pharmacology and GPCR modulation.<\/p>\n<h3>A Novel Serotonin Binding Pose<\/h3>\n<p>We showcase a newly obtained cryo-EM structure of the 5-HT2A receptor, which reveals a previously unprecedented serotonin binding confirmation. In contrast to earlier X-Ray crystallography models, this structure offers a pose that better reflects serotonin&rsquo;s expected pharmacological behaviour.<\/p>\n<p>Importantly, the complete receptor complex resolved via cryo-EM proved essential &#8211; without it, the previously reported crystallographic data may mislead subsequent ligand design and small molecule optimization efforts.<\/p>\n<h3>Supporting GPCR-Targeted CNS Discovery<\/h3>\n<p>At Sygnature Discovery, our <a href=\"https:\/\/www.sygnaturediscovery.com\/drug-discovery\/protein-science-and-structural-biology\/structural-biology\/\">structural biology team<\/a> provides expertise in cryo-EM, X-ray crystallography and NMR- working hand-in-hand with pharmacologist and chemists to translate structural insights into drug discovery outcomes.<\/p>\n<p><a href=\"https:\/\/www.sygnaturediscovery.com\/contact\/\">Contact our experts<\/a> to discuss your target structure or CNS program.<\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":2871,"template":"","category":[771,747,680,702,704,687],"class_list":["post-4136","poster","type-poster","status-publish","has-post-thumbnail","hentry","category-cryo-em","category-gpcrs","category-protein-and-structure","category-protein-expression-and-purification","category-structural-biology","category-target-classes"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Serotonin Binding at 5-HT2A via Cryo-EM<\/title>\n<meta name=\"description\" content=\"Download Sygnature Discovery&#039;s poster exploring the serotonin binding pose at the 5-HT2A receptor using cryo-EM.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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