{"id":"611090ce-ebb4-5b41-a06b-c02c15828261","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-binding-orientation","predicate":"orients","statement":"CYP2A6 Asn297 hydrogen bonding oriented coumarin within a compact hydrophobic active site for position-selective oxidation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7313f201-cd2c-5d8e-865f-1fc6afb7d27b","mechanism_event_label":"The enzyme holds coumarin in a specific orientation.","subject":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"object":{"id":"9fd9b93a-fdfd-5e09-92d3-0495bff41391","slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"7313f201-cd2c-5d8e-865f-1fc6afb7d27b","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-binding-orientation-event","event_type":"biochemical_relationship","label":"The enzyme holds coumarin in a specific orientation.","description":"CYP2A6 Asn297 hydrogen bonding oriented coumarin within a compact hydrophobic active site for position-selective oxidation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9fd9b93a-fdfd-5e09-92d3-0495bff41391","slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/coumarin-research/16086027.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d\", \"start_char\": 0, \"end_char\": 532, \"text_sha256\": \"df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"X-ray structures of ligand-bound human CYP2A6","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Coumarin and methoxsalen-bound structures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Structure demonstrates binding geometry, not clinical effects or dietary iron responsiveness.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Coumarin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The enzyme holds coumarin in a specific orientation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coumarin-p16086027] Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. (2005). https://pubmed.ncbi.nlm.nih.gov/16086027/ DOI: 10.1038/nsmb971","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CYP2A6 active site","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1e5952f7-9f5a-5d09-afd4-73f3afd78f8a","evidence_kind":"source_excerpt","locator":"Lines 163-174","start_line":163,"end_line":174,"excerpt":"### coumarin-binding-orientation\nCYP2A6 Asn297 hydrogen bonding oriented coumarin within a compact hydrophobic active site for position-selective oxidation.\nCondition category: normal\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The enzyme holds coumarin in a specific orientation.\norganism: Human protein\ntissue_or_cell_type: CYP2A6 active site\nexperimental_model: X-ray structures of ligand-bound human CYP2A6\nlimitations: Structure demonstrates binding geometry, not clinical effects or dietary iron responsiveness.\nexposure: Coumarin and methoxsalen-bound structures\nevidence_span: {\"source_cache\": \"artifacts/coumarin-research/16086027.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d\", \"start_char\": 0, \"end_char\": 532, \"text_sha256\": \"df98434feed879e206e54c520d496e9711581107f6aec58bd9dcc1c74ed5d49d\"}\n[coumarin-p16086027] Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. 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