{"id":"a9d36993-e525-5169-9f48-cac7a60eaf0e","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-aanat-dual-binding","predicate":"enhances_dual_phosphorylated","statement":"Binding involving both phosphorylated Thr31 and Ser205 lowered ovine AANAT substrate Km to about 30 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"468caf42-2c41-5cc8-81f7-3852d7f155ff","mechanism_event_label":"A regulatory partner can make the enzyme bind its substrate more effectively.","subject":{"id":"623c284c-fa20-5e91-918c-2b78dbd86bd4","slug":"aanat-binding-14-3-3-proteins","display_name":"14-3-3 proteins in AANAT biochemical experiments","entity_type_key":"protein_family"},"object":{"id":"6e5d0505-f306-5869-8e84-562087f257ef","slug":"aanat-catalytic-substrate-affinity","display_name":"AANAT arylalkylamine substrate affinity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"468caf42-2c41-5cc8-81f7-3852d7f155ff","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-aanat-dual-binding-event","event_type":"biochemical_relationship","label":"A regulatory partner can make the enzyme bind its substrate more effectively.","description":"Binding involving both phosphorylated Thr31 and Ser205 lowered ovine AANAT substrate Km to about 30 micromolar.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5f714613-61b0-5314-a31c-3267e614d83a","slug":"ovine-aanat","display_name":"Sheep arylalkylamine N-acetyltransferase / AANAT","entity_type_key":"protein"},"role":"regulated_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"623c284c-fa20-5e91-918c-2b78dbd86bd4","slug":"aanat-binding-14-3-3-proteins","display_name":"14-3-3 proteins in AANAT biochemical experiments","entity_type_key":"protein_family"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6e5d0505-f306-5869-8e84-562087f257ef","slug":"aanat-catalytic-substrate-affinity","display_name":"AANAT arylalkylamine substrate affinity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/15644438.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552\", \"start_char\": 0, \"end_char\": 1693, \"text_sha256\": \"d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Phosphorylation, binding and enzyme-kinetic experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Thr31 and Ser205 phosphorylation; night versus light exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation.","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":"Sheep AANAT and 14-3-3 biochemical systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A regulatory partner can make the enzyme bind its substrate more effectively.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Pineal enzyme regulation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"50b3fcc8-5ed1-54da-b3db-b8e8b5c01aa1","evidence_kind":"source_excerpt","locator":"Lines 240-251","start_line":240,"end_line":251,"excerpt":"### melatonin-aanat-dual-binding\nBinding involving both phosphorylated Thr31 and Ser205 lowered ovine AANAT substrate Km to about 30 micromolar.\nCondition category: normal\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A regulatory partner can make the enzyme bind its substrate more effectively.\norganism: Sheep AANAT and 14-3-3 biochemical systems\ntissue_or_cell_type: Pineal enzyme regulation\nexperimental_model: Phosphorylation, binding and enzyme-kinetic experiments\nlimitations: Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation.\nexposure: Thr31 and Ser205 phosphorylation; night versus light exposure\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/15644438.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552\", \"start_char\": 0, \"end_char\": 1693, \"text_sha256\": \"d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552\"}\n[melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102","model_system":"Phosphorylation, binding and enzyme-kinetic experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102","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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