{"id":"0600337c-afb7-53ab-8d2e-2ec567f56fdf","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-met-scly-specificity","predicate":"gains-activity-toward","statement":"Replacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"8180b4bf-59b0-5489-be53-2783bcc4a885","mechanism_event_label":"A specific enzyme residue helps distinguish selenium from sulfur substrates.","subject":{"id":"34d660e1-9adf-5f81-a5dd-6b76e926caa1","slug":"scly-d146k","display_name":"Human SCLY Asp146Lys variant","entity_type_key":"protein_state"},"object":{"id":"ca899f13-50ad-55e5-ab99-329ae0038c74","slug":"l-cysteine","display_name":"L-Cysteine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"8180b4bf-59b0-5489-be53-2783bcc4a885","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-met-scly-specificity-event","event_type":"biochemical_relationship","label":"A specific enzyme residue helps distinguish selenium from sulfur substrates.","description":"Replacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"34d660e1-9adf-5f81-a5dd-6b76e926caa1","slug":"scly-d146k","display_name":"Human SCLY Asp146Lys variant","entity_type_key":"protein_state"},"role":"engineered variant","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7c1bfe9f-559b-598e-9cca-8d0b032919fd","slug":"scly","display_name":"SCLY","entity_type_key":"protein"},"role":"wild-type comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ca899f13-50ad-55e5-ab99-329ae0038c74","slug":"l-cysteine","display_name":"L-Cysteine","entity_type_key":"small_molecule"},"role":"alternative substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"533add43-f6ba-5428-ab2d-74a45c054655","slug":"selenocysteine","display_name":"Sec","entity_type_key":"small_molecule"},"role":"native substrate","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human SCLY; structures and substrate assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered gain of function; physiological rates and clinical effects were not tested.","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":"A specific enzyme residue helps distinguish selenium from sulfur substrates.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581","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},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"20c08225-9eaf-5015-b40f-60eff83252a6","evidence_kind":"source_excerpt","locator":"Lines 937-947","start_line":937,"end_line":947,"excerpt":"### b6-met-scly-specificity\nReplacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A specific enzyme residue helps distinguish selenium from sulfur substrates.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant protein; no intact tissue\nexperimental_model: Recombinant human SCLY; structures and substrate assays\nlimitations: Engineered gain of function; physiological rates and clinical effects were not tested.\ncross_nutrient: Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme.\n[b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581","model_system":"Recombinant human SCLY; structures and substrate assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581","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}