{"id":"46983459-00af-5d79-9933-fbb3e0fceb86","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lias-two-clusters","predicate":"requires","statement":"LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8f73f4d8-0b90-5bfc-a51e-dcaa79da22c0","mechanism_event_label":"Two iron-sulfur clusters perform different jobs in the same enzyme.","subject":{"id":"f9fc9417-ca4f-5e0c-b01d-60b337493d34","slug":"lias","display_name":"Lipoic acid synthetase / LIAS","entity_type_key":"protein"},"object":{"id":"8058ae47-b091-5004-ba65-1e50ad91f70b","slug":"iron-sulfur-4fe4s","display_name":"[4Fe-4S] iron-sulfur cluster","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"8f73f4d8-0b90-5bfc-a51e-dcaa79da22c0","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lias-two-clusters-event","event_type":"biochemical_relationship","label":"Two iron-sulfur clusters perform different jobs in the same enzyme.","description":"LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"372bf9a1-150b-5492-87c3-853a7d9b96e7","slug":"lias-radical-sam-cluster-state","display_name":"LIAS radical-SAM [4Fe-4S] site","entity_type_key":"protein_state"},"role":"radical_generation_site","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"65497586-1f6a-5981-a0b1-784ecb5e849f","slug":"lias-auxiliary-cluster-state","display_name":"LIAS auxiliary [4Fe-4S] site","entity_type_key":"protein_state"},"role":"sulfur_donor_site","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f9fc9417-ca4f-5e0c-b01d-60b337493d34","slug":"lias","display_name":"Lipoic acid synthetase / LIAS","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8058ae47-b091-5004-ba65-1e50ad91f70b","slug":"iron-sulfur-4fe4s","display_name":"[4Fe-4S] iron-sulfur cluster","entity_type_key":"chemical_species"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ala-research/36281303.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f\", \"start_char\": 0, \"end_char\": 1732, \"text_sha256\": \"29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human LIAS turnover and cluster-transfer assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"LIAS with candidate iron-sulfur cluster donors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human recombinant proteins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Two iron-sulfur clusters perform different jobs in the same enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mitochondrial lipoyl synthesis machinery","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9c8b5778-0513-56e3-a9d0-0e1307fa7c45","evidence_kind":"source_excerpt","locator":"Lines 299-310","start_line":299,"end_line":310,"excerpt":"### ala-lias-two-clusters\nLIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Two iron-sulfur clusters perform different jobs in the same enzyme.\norganism: Human recombinant proteins\ntissue_or_cell_type: Mitochondrial lipoyl synthesis machinery\nexperimental_model: Purified human LIAS turnover and cluster-transfer assays\nlimitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.\nexposure: LIAS with candidate iron-sulfur cluster donors\nevidence_span: {\"source_cache\": \"artifacts/ala-research/36281303.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f\", \"start_char\": 0, \"end_char\": 1732, \"text_sha256\": \"29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f\"}\n[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. 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