{"id":"8f0d9f78-82a0-5977-aeda-bbf9feed0030","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-mocos-r776c","predicate":"impairs_binding_of","statement":"MOCOS Arg776Cys impaired cofactor binding in the C-terminal domain assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"bb533ed7-d42f-5db8-a725-dc77a8c459b3","mechanism_event_label":"A second variant damages the same cofactor-handling stage.","subject":{"id":"914d892c-7abd-5e19-82d4-0640e106e1a0","slug":"mocos-r776c","display_name":"Human MOCOS p.Arg776Cys","entity_type_key":"protein_state"},"object":{"id":"ac4bcc03-66fb-52c1-b191-9ecb2124659f","slug":"molybdenum-cofactor","display_name":"Molybdenum cofactor / Moco","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"bb533ed7-d42f-5db8-a725-dc77a8c459b3","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-mocos-r776c-event","event_type":"biochemical_relationship","label":"A second variant damages the same cofactor-handling stage.","description":"MOCOS Arg776Cys impaired cofactor binding in the C-terminal domain assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"914d892c-7abd-5e19-82d4-0640e106e1a0","slug":"mocos-r776c","display_name":"Human MOCOS p.Arg776Cys","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ac4bcc03-66fb-52c1-b191-9ecb2124659f","slug":"molybdenum-cofactor","display_name":"Molybdenum cofactor / Moco","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/molybdenum-research/34356852.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9a7e4ebde1063db92cef7c8b18753b2d2af12f8f132cad45fc2e3ae00b911f96\", \"start_char\": 0, \"end_char\": 1697, \"text_sha256\": \"9a7e4ebde1063db92cef7c8b18753b2d2af12f8f132cad45fc2e3ae00b911f96\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"PLP quantification, cysteine desulfurase assays and Moco/MPT binding","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Molybdenum research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"molybdenum","display_name":"Molybdenum","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human genetics and human MOCOS proteins; plant XDH variant experiment separately","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A second variant damages the same cofactor-handling stage.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient samples and purified domains","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":"b32fd0e0-13d7-5e32-879c-bc6e89257f9b","evidence_kind":"source_excerpt","locator":"Lines 573-584","start_line":573,"end_line":584,"excerpt":"### mo-mocos-r776c\nMOCOS Arg776Cys impaired cofactor binding in the C-terminal domain assay.\nCondition category: machinery_impairment\nnutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A second variant damages the same cofactor-handling stage.\norganism: Human genetics and human MOCOS proteins; plant XDH variant experiment separately\ntissue_or_cell_type: Patient samples and purified domains\nexperimental_model: Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay\nlimitations: Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains.\nexposure: PLP quantification, cysteine desulfurase assays and Moco/MPT binding\nevidence_span: {\"source_cache\": \"artifacts/molybdenum-research/34356852.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9a7e4ebde1063db92cef7c8b18753b2d2af12f8f132cad45fc2e3ae00b911f96\", \"start_char\": 0, \"end_char\": 1697, \"text_sha256\": \"9a7e4ebde1063db92cef7c8b18753b2d2af12f8f132cad45fc2e3ae00b911f96\"}\n[mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. 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