{"id":"009dc178-3131-53e2-bd7b-73e93fa36abd","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-met-alas2-plp","predicate":"binds-to","statement":"The human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"64db3e98-b9bd-5db9-90ed-2e12ebfb48b9","mechanism_event_label":"Active B6 is bound inside the erythroid heme-precursor enzyme.","subject":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"object":{"id":"c427a619-825d-5675-9923-3b5b84769f0f","slug":"alas2","display_name":"Human erythroid aminolevulinate synthase 2 / ALAS2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"64db3e98-b9bd-5db9-90ed-2e12ebfb48b9","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-met-alas2-plp-event","event_type":"biochemical_relationship","label":"Active B6 is bound inside the erythroid heme-precursor enzyme.","description":"The human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"c427a619-825d-5675-9923-3b5b84769f0f","slug":"alas2","display_name":"Human erythroid aminolevulinate synthase 2 / ALAS2","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"B6-dependent production of precursors for iron-containing heme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified recombinant human ALAS2; crystallography and kinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b6","display_name":"Vitamin B6","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Active B6 is bound inside the erythroid heme-precursor enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x","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":"3d48ff98-0b18-5bc2-9c54-8a2d347d1c89","evidence_kind":"source_excerpt","locator":"Lines 787-797","start_line":787,"end_line":797,"excerpt":"### b6-met-alas2-plp\nThe human ALAS2 structure positions PLP at the catalytic dimer interface with its covalent attachment to Lys391.\nCondition category: normal\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Active B6 is bound inside the erythroid heme-precursor enzyme.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant protein; no intact tissue\nexperimental_model: Purified recombinant human ALAS2; crystallography and kinetics\nlimitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.\ncross_nutrient: B6-dependent production of precursors for iron-containing heme.\n[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x","model_system":"Purified recombinant human ALAS2; crystallography and kinetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"251773bb-16f5-5903-b135-db4a61d9dec4","stable_key":"import-1310afbd-6010-586e-805d-551d846da421","title":"Vitamin B6: mechanisms, deficiency 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":"ef0019b344b2219220f801a84d0d138ff6880c1be1a59540d9034bfa4334f61e","revision_id":"cac3555f-48af-5c52-a84e-add4482c87fb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}