{"id":"82e83085-6540-53ab-951f-71122f45691c","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-dhtkd1-r715c-dlst-binding","predicate":"reduces-association-with","statement":"The human DHTKD1 Arg715Cys variant impaired DLST interaction in recombinant complex-formation experiments.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e8f93231-3213-5e95-bcca-e626e95453f9","mechanism_event_label":"Having the B1-dependent protein is not enough if it cannot join its downstream partner.","subject":{"id":"e93fdaec-7162-5e1f-913b-4e53bfdc2998","slug":"dhtkd1-r715c","display_name":"DHTKD1 Arg715Cys","entity_type_key":"protein_state"},"object":{"id":"6d9c0f10-8013-5379-bc6f-d51367718dec","slug":"dlst","display_name":"DLST","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"e8f93231-3213-5e95-bcca-e626e95453f9","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-dhtkd1-r715c-dlst-binding-event","event_type":"biochemical_relationship","label":"Having the B1-dependent protein is not enough if it cannot join its downstream partner.","description":"The human DHTKD1 Arg715Cys variant impaired DLST interaction in recombinant complex-formation experiments.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"b8552ee2-4a84-59a0-9694-69991c9903bf","slug":"dhtkd1","display_name":"DHTKD1","entity_type_key":"protein"},"role":"wild-type comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e93fdaec-7162-5e1f-913b-4e53bfdc2998","slug":"dhtkd1-r715c","display_name":"DHTKD1 Arg715Cys","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6d9c0f10-8013-5379-bc6f-d51367718dec","slug":"dlst","display_name":"DLST","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence","value_text":"[{\"paper_key\": \"bezerra-2020-dhtkd1\", \"source_bundle\": \"artifacts/thiamine_metabolism_sources.json\", \"passage_ids\": [\"p-59\", \"p-61\", \"p-63\", \"p-64\"], \"locator\": \"R715C\", \"preservation\": \"Exact text retained in the source bundle; full source document retained when openly retrievable.\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant variant interaction assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Variant-specific assembly result; no thiamine rescue claim.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Thiamine (vitamin B1)","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Having the B1-dependent protein is not enough if it cannot join its downstream partner.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified proteins","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":"6d43868e-8bfc-57dd-9f26-13f25a4d7ae3","evidence_kind":"source_excerpt","locator":"Lines 923-934","start_line":923,"end_line":934,"excerpt":"### b1-dhtkd1-r715c-dlst-binding\nThe human DHTKD1 Arg715Cys variant impaired DLST interaction in recombinant complex-formation experiments.\nCondition category: machinery_impairment\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Having the B1-dependent protein is not enough if it cannot join its downstream partner.\norganism: Homo sapiens\ntissue_or_cell_type: Purified proteins\nexperimental_model: Recombinant variant interaction assays.\nlimitations: Variant-specific assembly result; no thiamine rescue claim.\nevidence: [{\"paper_key\": \"bezerra-2020-dhtkd1\", \"source_bundle\": \"artifacts/thiamine_metabolism_sources.json\", \"passage_ids\": [\"p-59\", \"p-61\", \"p-63\", \"p-64\"], \"locator\": \"R715C\", \"preservation\": \"Exact text retained in the source bundle; full source document retained when openly retrievable.\"}]\nnutrient: Thiamine (vitamin B1)\n[bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x","model_system":"Recombinant variant interaction assays.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"158d2c03-ac8c-589f-8270-c468165ae346","stable_key":"import-46d15d9e-d3b5-544d-ba01-b785aa3e4f42","title":"Thiamine: 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":"f376512fb3310141315548015b387833e3af45146e73fb73cd02cee20e4ddb9c","revision_id":"53bc5eda-dec8-58cc-a56f-a9eb4ab036ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}