{"id":"ee7c8ef6-c499-50b5-b846-04539ac07782","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-aoc1-copper-tpq","predicate":"contains_catalytic","statement":"Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"28e10dff-0ba9-5e45-bf3b-2bffb1341740","mechanism_event_label":"Histamine-processing machinery includes both a metal and a protein-derived cofactor.","subject":{"id":"817bfd3f-5c75-53e7-8a27-5b80cf0a603b","slug":"aoc1","display_name":"Human diamine oxidase / AOC1 / DAO","entity_type_key":"protein"},"object":{"id":"6dd387e0-1f91-5bef-8e84-c7bfabce7e9a","slug":"topaquinone-cofactor","display_name":"Protein-derived topaquinone / TPQ cofactor","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"28e10dff-0ba9-5e45-bf3b-2bffb1341740","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-aoc1-copper-tpq-event","event_type":"biochemical_relationship","label":"Histamine-processing machinery includes both a metal and a protein-derived cofactor.","description":"Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9f0afdde-1ec1-5c8a-bb5e-f3b2b75f67f6","slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"},"role":"enzyme-bound metal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"817bfd3f-5c75-53e7-8a27-5b80cf0a603b","slug":"aoc1","display_name":"Human diamine oxidase / AOC1 / DAO","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6dd387e0-1f91-5bef-8e84-c7bfabce7e9a","slug":"topaquinone-cofactor","display_name":"Protein-derived topaquinone / TPQ cofactor","entity_type_key":"chemical_species"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/copper-research/19764817.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6\", \"start_char\": 0, \"end_char\": 1343, \"text_sha256\": \"9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Crystallography of recombinant human diamine oxidase and inhibitor complexes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Native structure and inhibitor binding","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Copper research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human AOC1 expressed in insect cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Histamine-processing machinery includes both a metal and a protein-derived cofactor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p19764817] Structure and inhibition of human diamine oxidase. (2009). https://pubmed.ncbi.nlm.nih.gov/19764817/ DOI: 10.1021/bi9014192","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified protein","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"69f7f8d1-45fa-5a6c-89ad-0d4787ce5e07","evidence_kind":"source_excerpt","locator":"Lines 1014-1025","start_line":1014,"end_line":1025,"excerpt":"### copper-aoc1-copper-tpq\nHuman AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites.\nCondition category: normal\nnutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Histamine-processing machinery includes both a metal and a protein-derived cofactor.\norganism: Human AOC1 expressed in insect cells\ntissue_or_cell_type: Purified protein\nexperimental_model: Crystallography of recombinant human diamine oxidase and inhibitor complexes\nlimitations: Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants.\nexposure: Native structure and inhibitor binding\nevidence_span: {\"source_cache\": \"artifacts/copper-research/19764817.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6\", \"start_char\": 0, \"end_char\": 1343, \"text_sha256\": \"9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6\"}\n[copper-p19764817] Structure and inhibition of human diamine oxidase. 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