{"id":"50c518ce-b0d6-566d-acb8-fad2de7a22c6","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-tdo-heme-oxygen","predicate":"cofactor-for","statement":"In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"16b54aeb-6757-551b-844a-528aa51f4869","mechanism_event_label":"Iron held in heme positions oxygen for this precursor reaction.","subject":{"id":"2e1f7e0a-8b54-5ea3-9d34-01e7167f9097","slug":"heme","display_name":"Heme","entity_type_key":"small_molecule"},"object":{"id":"069155e2-e27b-55c2-85e3-b4a96bc91876","slug":"tdo2","display_name":"Human tryptophan 2,3-dioxygenase / TDO2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"16b54aeb-6757-551b-844a-528aa51f4869","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-tdo-heme-oxygen-event","event_type":"biochemical_relationship","label":"Iron held in heme positions oxygen for this precursor reaction.","description":"In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"069155e2-e27b-55c2-85e3-b4a96bc91876","slug":"tdo2","display_name":"Human tryptophan 2,3-dioxygenase / TDO2","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2e1f7e0a-8b54-5ea3-9d34-01e7167f9097","slug":"heme","display_name":"Heme","entity_type_key":"small_molecule"},"role":"iron-containing prosthetic group","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"899c7ab0-6f81-5b38-a6bd-fbb33d66ac8d","slug":"oxygen","display_name":"Molecular oxygen","entity_type_key":"small_molecule"},"role":"coordinated substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 7–7 (0-based)\", \"start_char\": 5512, \"end_char\": 7250, \"file_sha256\": \"3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5\", \"text_sha256\": \"057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human TDO2 crystallography and spectroscopy; substrate/product complexes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Biochemical or structural assay; no dietary intervention","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Niacin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"niacin","display_name":"Niacin (vitamin B3)","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Iron held in heme positions oxygen for this precursor reaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified recombinant protein; no intact tissue","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e90ed4e5-2a94-54f5-a256-322da5a325e0","evidence_kind":"source_excerpt","locator":"Lines 493-505","start_line":493,"end_line":505,"excerpt":"### b3-pre-tdo-heme-oxygen\nIn the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate.\nCondition category: normal\nnutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Iron held in heme positions oxygen for this precursor reaction.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant protein; no intact tissue\nexperimental_model: Purified human TDO2 crystallography and spectroscopy; substrate/product complexes\nlimitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.\nexposure: Biochemical or structural assay; no dietary intervention\ncross_nutrient: Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold.\nevidence_span: {\"source_cache\": \"artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 7–7 (0-based)\", \"start_char\": 5512, \"end_char\": 7250, \"file_sha256\": \"3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5\", \"text_sha256\": \"057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0\"}\n[b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. 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