{"id":"b8656087-3091-52a0-8678-0872f8154ea2","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-tph1-iron","predicate":"coordinates_substrate_near","statement":"The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"104fc80b-b915-5407-bab5-3b958f8b8a5c","mechanism_event_label":"The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin.","subject":{"id":"52d66ced-4bbe-567f-a641-b72b2c038b93","slug":"tph1","display_name":"Human tryptophan hydroxylase 1 / TPH1","entity_type_key":"protein"},"object":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"evidence_count":1,"mechanism_event":{"id":"104fc80b-b915-5407-bab5-3b958f8b8a5c","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-tph1-iron-event","event_type":"biochemical_relationship","label":"The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin.","description":"The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron.","status":"provisional","compartment":null,"participants":[{"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":0,"notes":""},{"entity":{"id":"3eda9053-4a47-50b7-838d-d185b01a4355","slug":"dihydrobiopterin","display_name":"7,8-Dihydrobiopterin / BH2","entity_type_key":"small_molecule"},"role":"structural_analogue","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"52d66ced-4bbe-567f-a641-b72b2c038b93","slug":"tph1","display_name":"Human tryptophan hydroxylase 1 / TPH1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/11747434.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06\", \"start_char\": 0, \"end_char\": 2063, \"text_sha256\": \"c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"NMR substrate/cofactor geometry and enzyme modeling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"L-tryptophan and bound BH2 cofactor analogue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Melatonin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Recombinant human TPH1 catalytic domain","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Non-heme iron active site","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"097fae2b-9418-570c-8cfe-22cac74e7399","evidence_kind":"source_excerpt","locator":"Lines 162-173","start_line":162,"end_line":173,"excerpt":"### melatonin-tph1-iron\nThe human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron.\nCondition category: normal\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin.\norganism: Recombinant human TPH1 catalytic domain\ntissue_or_cell_type: Non-heme iron active site\nexperimental_model: NMR substrate/cofactor geometry and enzyme modeling\nlimitations: BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured.\nexposure: L-tryptophan and bound BH2 cofactor analogue\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/11747434.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06\", \"start_char\": 0, \"end_char\": 2063, \"text_sha256\": \"c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06\"}\n[melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x","model_system":"NMR substrate/cofactor geometry and enzyme modeling","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"bab588de-d217-5038-9c8b-b41222eba08b","stable_key":"import-3279ff78-2460-5064-bfc0-3f2987af85a0","title":"Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"ff4f279d263f95a69da8e7e8a6c6318ab6ba1b55254dbbda1bfa9ce437e1db80","revision_id":"0318eef8-ff38-513e-8ffa-458146ca5e77","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}