{"id":"7816e3a0-5baa-57b1-ba94-20595b8afce0","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipoyl-lysine-anchor","predicate":"is_covalently_attached_to","statement":"The lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2780630b-e3b9-5791-ad1b-a1360725a023","mechanism_event_label":"The enzyme uses a tethered cofactor; free supplement molecules are a different pool.","subject":{"id":"fd2197c3-5a63-55f4-8bb1-bfc1e91a0e1e","slug":"protein-bound-lipoamide","display_name":"Protein-bound oxidized lipoyl-lysine","entity_type_key":"chemical_species"},"object":{"id":"78a93278-7e43-59c7-b097-31bbae21c771","slug":"gcsh","display_name":"Human glycine-cleavage H-protein / GCSH","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2780630b-e3b9-5791-ad1b-a1360725a023","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipoyl-lysine-anchor-event","event_type":"biochemical_relationship","label":"The enzyme uses a tethered cofactor; free supplement molecules are a different pool.","description":"The lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"280f29ca-25cf-57bb-92b9-ffc43ca11373","slug":"gcsh-lipoyl","display_name":"Human lipoyl-GCSH","entity_type_key":"protein_state"},"role":"protein_bound_state","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fd2197c3-5a63-55f4-8bb1-bfc1e91a0e1e","slug":"protein-bound-lipoamide","display_name":"Protein-bound oxidized lipoyl-lysine","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"78a93278-7e43-59c7-b097-31bbae21c771","slug":"gcsh","display_name":"Human glycine-cleavage H-protein / GCSH","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ala-research/40640146.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23\", \"start_char\": 0, \"end_char\": 953, \"text_sha256\": \"292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"X-ray structures of catalytic stages with human lipoyl synthase","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Structural trapping of sulfur-insertion intermediates","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Structural snapshots establish reaction intermediates, not clinical nutrient requirements.","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":"The enzyme uses a tethered cofactor; free supplement molecules are a different pool.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"LIAS and H-protein substrate","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9acee159-becb-5387-8142-60a26b2a9933","evidence_kind":"source_excerpt","locator":"Lines 247-258","start_line":247,"end_line":258,"excerpt":"### ala-lipoyl-lysine-anchor\nThe lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The enzyme uses a tethered cofactor; free supplement molecules are a different pool.\norganism: Human recombinant proteins\ntissue_or_cell_type: LIAS and H-protein substrate\nexperimental_model: X-ray structures of catalytic stages with human lipoyl synthase\nlimitations: Structural snapshots establish reaction intermediates, not clinical nutrient requirements.\nexposure: Structural trapping of sulfur-insertion intermediates\nevidence_span: {\"source_cache\": \"artifacts/ala-research/40640146.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23\", \"start_char\": 0, \"end_char\": 953, \"text_sha256\": \"292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23\"}\n[ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x","model_system":"X-ray structures of catalytic stages with human lipoyl synthase","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d8afa8c2-ced9-5b28-90ca-2ac120ec7202","stable_key":"import-5d8e27d8-6a74-5560-827f-3f90908bbc34","title":"Alpha-lipoic acid: cofactor assembly, redox signaling 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":"611da198ab85a272eb26b64ee330ef6d1a762853a8481f3191c4acfca9f3cf3d","revision_id":"618b4ce6-3157-5222-8325-408064be5ea5","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}