{"id":"e822a805-469e-5acd-a294-58382fe1b494","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:atorvastatin-hmgcr-occupancy","predicate":"inhibits","statement":"Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"2b4d6546-dfee-5bff-8829-53a947b5100e","mechanism_event_label":"Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.","subject":{"id":"64f4b2c7-afdf-5b9a-b6f9-015a7aa96eee","slug":"atorvastatin","display_name":"Atorvastatin","entity_type_key":"small_molecule"},"object":{"id":"a8b5e5e1-b5b5-551d-8fd4-72f7b45de78a","slug":"hmgcr","display_name":"HMG-CoA reductase (HMGCR)","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2b4d6546-dfee-5bff-8829-53a947b5100e","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:atorvastatin-hmgcr-occupancy-event","event_type":"observed_relationship","label":"Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.","description":"Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"64f4b2c7-afdf-5b9a-b6f9-015a7aa96eee","slug":"atorvastatin","display_name":"Atorvastatin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a8b5e5e1-b5b5-551d-8fd4-72f7b45de78a","slug":"hmgcr","display_name":"HMG-CoA reductase (HMGCR)","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3df322fd-ac21-5bd1-aa46-4af1ec708b57","slug":"mevalonate","display_name":"Mevalonate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"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":"Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Statin-enzyme complexes, inhibition constants in the nanomolar range","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Structural","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Enzyme active-site occupancy","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"a55bb975-42d0-5acd-a00e-e2de85a93d4c","evidence_kind":"source_excerpt","locator":"Lines 13-22","start_line":13,"end_line":22,"excerpt":"## atorvastatin-hmgcr-occupancy\nStatins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.\nModel/species: Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins\nTissue/system: Enzyme active-site occupancy\nExposure: Statin-enzyme complexes, inhibition constants in the nanomolar range\nRoute: Structural\nDuration: Not applicable\nLimits: The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes.\nPrimary reference: Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344\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":"a4431d8c-34d7-5db7-9edf-a35f68feba39","stable_key":"import-1fb6218a-60d1-55ea-87fe-07d15d0fc46f","title":"Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"6307f1acf99f90662320328974781ee660348754257b1e1555701ad597edc8e5","revision_id":"447c5978-ba3f-58fe-ac85-664caa72e01b","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}