{"id":"87644bfa-df68-52cb-8895-b10d0665be3f","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-mmad-t182n-complex","predicate":"reduces-binding-to","statement":"Human MMADHC delta123 carrying T182N showed strongly reduced complex formation with full-length human MMACHC after MeCbl/GSH incubation, compared with matched delta123 MMADHC.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"4eb5e841-ab50-5c51-b930-9a0ade420526","mechanism_event_label":"This variant disrupted the two processing proteins’ association.","subject":{"id":"2597be23-a9db-5be2-8a95-c4c9544203ef","slug":"mmadhc-delta123-t182n","display_name":"Human MMADHC delta123 T182N","entity_type_key":"protein_state"},"object":{"id":"70ae4c83-37b2-5bd7-931d-021cace41eef","slug":"mmachc","display_name":"Human MMACHC / cobalamin-processing protein CblC","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"4eb5e841-ab50-5c51-b930-9a0ade420526","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-mmad-t182n-complex-event","event_type":"biochemical_relationship","label":"This variant disrupted the two processing proteins’ association.","description":"Human MMADHC delta123 carrying T182N showed strongly reduced complex formation with full-length human MMACHC after MeCbl/GSH incubation, compared with matched delta123 MMADHC.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"processing co-substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6563fbad-ebdc-5408-966a-d24f8b8cd854","slug":"methylcobalamin","display_name":"Methylcobalamin","entity_type_key":"small_molecule"},"role":"starting cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"88c49063-bdbd-5fdd-bfe1-da1541c79c8f","slug":"mmachc-mmadhc-cobalamin-complex","display_name":"Human MMACHC–MMADHC cobalamin coordination complex","entity_type_key":"protein_complex"},"role":"measured assembly","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2597be23-a9db-5be2-8a95-c4c9544203ef","slug":"mmadhc-delta123-t182n","display_name":"Human MMADHC delta123 T182N","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"70ae4c83-37b2-5bd7-931d-021cace41eef","slug":"mmachc","display_name":"Human MMACHC / cobalamin-processing protein CblC","entity_type_key":"protein"},"role":"target","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":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Results: Figure 5D; Experimental Procedures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human proteins; blue-native PAGE","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"T182N versus matched delta123 comparator, MMACHC, MeCbl and GSH","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Functional assay used human proteins; mouse MMADHC was used for the separate crystal structure. Truncation may affect full-length behavior.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This variant disrupted the two processing proteins’ association.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[froese-2015-complex] Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking (2015). https://pubmed.ncbi.nlm.nih.gov/26483544/ DOI: 10.1074/jbc.M115.683268","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free assay","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":"dd7a65f3-9ce3-5236-872a-36fb3158a4a9","evidence_kind":"source_excerpt","locator":"Lines 865-877","start_line":865,"end_line":877,"excerpt":"### b12-mmad-t182n-complex\nHuman MMADHC delta123 carrying T182N showed strongly reduced complex formation with full-length human MMACHC after MeCbl/GSH incubation, compared with matched delta123 MMADHC.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This variant disrupted the two processing proteins’ association.\norganism: Homo sapiens\ntissue_or_cell_type: Cell-free assay\nexperimental_model: Recombinant human proteins; blue-native PAGE\nlimitations: Functional assay used human proteins; mouse MMADHC was used for the separate crystal structure. Truncation may affect full-length behavior.\nexposure: T182N versus matched delta123 comparator, MMACHC, MeCbl and GSH\ncross_nutrient: false\nevidence_location: Results: Figure 5D; Experimental Procedures\n[froese-2015-complex] Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking (2015). https://pubmed.ncbi.nlm.nih.gov/26483544/ DOI: 10.1074/jbc.M115.683268","model_system":"Recombinant human proteins; blue-native PAGE","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [froese-2015-complex] Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking (2015). https://pubmed.ncbi.nlm.nih.gov/26483544/ DOI: 10.1074/jbc.M115.683268","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: 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":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}