{"id":"35036a8d-c082-5743-afdc-14ae76efc2df","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:pde5-binding-site-resolved-with-tadalafil","predicate":"binds","statement":"Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"b9689758-67bf-5a20-8611-b77324816a50","mechanism_event_label":"Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.","subject":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"object":{"id":"0be8b435-6b8a-592c-bd4c-c0efd9481a97","slug":"pde5-family","display_name":"Phosphodiesterase 5 family","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"b9689758-67bf-5a20-8611-b77324816a50","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:pde5-binding-site-resolved-with-tadalafil-event","event_type":"observed_relationship","label":"Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.","description":"Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0be8b435-6b8a-592c-bd4c-c0efd9481a97","slug":"pde5-family","display_name":"Phosphodiesterase 5 family","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fe62cf8d-5f89-5e19-bc36-03ad3c9063b7","slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"debc9521-fc5c-5c06-8c62-11cd34787c44","slug":"vardenafil","display_name":"Vardenafil","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not applicable","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human PDE5 catalytic domain","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Each of the three drug molecules complexed with the enzyme","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The catalytic domain alone was crystallised, not the full-length regulated enzyme, so the structures do not describe the allosteric cGMP-binding GAF domains.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human PDE5 catalytic domain","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. (2003). https://pubmed.ncbi.nlm.nih.gov/12955149/ DOI: 10.1038/nature01914","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Structural","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Inhibitor binding at the catalytic site","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0138aa38-c19e-55f1-a00a-6c404e9cca24","evidence_kind":"source_excerpt","locator":"Lines 35-44","start_line":35,"end_line":44,"excerpt":"## pde5-binding-site-resolved-with-tadalafil\nThree-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.\nModel/species: Human PDE5 catalytic domain\nTissue/system: Inhibitor binding at the catalytic site\nExposure: Each of the three drug molecules complexed with the enzyme\nRoute: Structural\nDuration: Not applicable\nLimits: The catalytic domain alone was crystallised, not the full-length regulated enzyme, so the structures do not describe the allosteric cGMP-binding GAF domains.\nPrimary reference: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. (2003). https://pubmed.ncbi.nlm.nih.gov/12955149/ DOI: 10.1038/nature01914\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"cca24ae7-e036-525c-a440-4cc2e38ccb4d","stable_key":"import-8ccb5461-efe2-5d95-9869-950d7cd50575","title":"Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text.","file_path":"","sha256":"3df8ec8f7114f983e8cae9fbc54912d3ac5b5f962454afea9dd8d4438c94cded","revision_id":"510acdea-65ae-57a6-b743-68e031ff1f05","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}