{"id":"61ceed4f-8b81-5eef-8f0d-8d3c0380bcdd","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-nqo2-cosubstrate-competition","predicate":"competitively_inhibits","statement":"Melatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4189bf44-6d9f-56c2-8216-8a86fc47c119","mechanism_event_label":"A redox enzyme is a distinct target from the high-affinity membrane receptors.","subject":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"object":{"id":"1c48fce8-58ed-5238-bdfc-6ce3924f20a7","slug":"nqo2","display_name":"Human quinone reductase 2 / NQO2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"4189bf44-6d9f-56c2-8216-8a86fc47c119","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-nqo2-cosubstrate-competition-event","event_type":"biochemical_relationship","label":"A redox enzyme is a distinct target from the high-affinity membrane receptors.","description":"Melatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"02dba9f5-2e7d-53d4-856b-53eb1fb4e1b5","slug":"n-methyldihydronicotinamide","display_name":"N-Methyldihydronicotinamide, NQO2 assay cosubstrate","entity_type_key":"small_molecule"},"role":"competing_assay_cosubstrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"1c48fce8-58ed-5238-bdfc-6ce3924f20a7","slug":"nqo2","display_name":"Human quinone reductase 2 / NQO2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/18254726.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18\", \"start_char\": 0, \"end_char\": 1724, \"text_sha256\": \"4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Kinetics, calorimetry and crystal structures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations.","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":"Purified human NQO2/QR2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A redox enzyme is a distinct target from the high-affinity membrane receptors.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cytosolic quinone-reductase active site","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8a037443-d7a6-56af-b0e1-46316c8554b5","evidence_kind":"source_excerpt","locator":"Lines 487-498","start_line":487,"end_line":498,"excerpt":"### melatonin-nqo2-cosubstrate-competition\nMelatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar.\nCondition category: normal\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A redox enzyme is a distinct target from the high-affinity membrane receptors.\norganism: Purified human NQO2/QR2\ntissue_or_cell_type: Cytosolic quinone-reductase active site\nexperimental_model: Kinetics, calorimetry and crystal structures\nlimitations: NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations.\nexposure: Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/18254726.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18\", \"start_char\": 0, \"end_char\": 1724, \"text_sha256\": \"4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18\"}\n[melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373","model_system":"Kinetics, calorimetry and crystal structures","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373","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. 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