{"id":"ede7f79e-6a15-55a8-a474-b8cf32951043","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-sod1-disulfide-independent","predicate":"can_oxidize_disulfide_without_copper_loading_in","statement":"In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"821abe34-a2ee-549f-8630-ce329177cff7","mechanism_event_label":"CCS can help form the SOD1 disulfide before copper is inserted.","subject":{"id":"51c0049d-9305-553a-ba5d-c1d3b1074801","slug":"ccs","display_name":"Human copper chaperone for SOD1 / CCS","entity_type_key":"protein"},"object":{"id":"a2f18cf0-b9dd-5ba2-962f-e76ac8dbaa2c","slug":"sod1-zinc-bound-reduced","display_name":"Zinc-bound disulfide-reduced human SOD1","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"821abe34-a2ee-549f-8630-ce329177cff7","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-sod1-disulfide-independent-event","event_type":"biochemical_relationship","label":"CCS can help form the SOD1 disulfide before copper is inserted.","description":"In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"19f2bdc0-4888-57d5-860f-119d5d478eb4","slug":"sod1","display_name":"Human copper-zinc superoxide dismutase / SOD1","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"bound_cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"162020b5-1fa5-526e-8405-452891245722","slug":"copper-i","display_name":"Copper(I) ion","entity_type_key":"ion"},"role":"not_required_for_this_observed_step","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"51c0049d-9305-553a-ba5d-c1d3b1074801","slug":"ccs","display_name":"Human copper chaperone for SOD1 / CCS","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"a2f18cf0-b9dd-5ba2-962f-e76ac8dbaa2c","slug":"sod1-zinc-bound-reduced","display_name":"Zinc-bound disulfide-reduced human SOD1","entity_type_key":"protein_state"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"CCS can help form the SOD1 disulfide before copper is inserted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human HEK293T cytoplasm","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"60a5af9e-b51c-5089-8aa7-2fc2e2c65159","evidence_kind":"source_excerpt","locator":"Lines 755-766","start_line":755,"end_line":766,"excerpt":"### zinc-enz-sod1-disulfide-independent\nIn zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading.\nCondition category: normal\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: CCS can help form the SOD1 disulfide before copper is inserted.\norganism: Homo sapiens\ntissue_or_cell_type: Human HEK293T cytoplasm\nexperimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR\nlimitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell.\nexposure: 10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison.\ncross_nutrient: true\n[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202","model_system":"Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, 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":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}