{"id":"508bd721-d0b9-513c-9af4-bc60485e3e91","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-methyl-sah-active-state","predicate":"accompanies_open_state_of","statement":"Single SAH occupancy accompanied a flexible catalytic domain with an exposed active site in human MTHFR structures.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"627a222b-327a-5f50-a17b-e68a8f1524ea","mechanism_event_label":"The SAH-bound structure leaves the catalytic site accessible.","subject":{"id":"e84829b1-0607-558e-8add-aaa3af4747e7","slug":"s-adenosylhomocysteine","display_name":"S-Adenosyl-L-homocysteine","entity_type_key":"small_molecule"},"object":{"id":"9fc32b1a-0f08-544c-a361-1c728203b6ec","slug":"mthfr","display_name":"Methylenetetrahydrofolate reductase / MTHFR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"627a222b-327a-5f50-a17b-e68a8f1524ea","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-methyl-sah-active-state-event","event_type":"biochemical_relationship","label":"The SAH-bound structure leaves the catalytic site accessible.","description":"Single SAH occupancy accompanied a flexible catalytic domain with an exposed active site in human MTHFR structures.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e84829b1-0607-558e-8add-aaa3af4747e7","slug":"s-adenosylhomocysteine","display_name":"S-Adenosyl-L-homocysteine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9fc32b1a-0f08-544c-a361-1c728203b6ec","slug":"mthfr","display_name":"Methylenetetrahydrofolate reductase / MTHFR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Recombinant human MTHFR; cryo-EM and biochemistry.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not imply SAH promotes all methyltransferases.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The SAH-bound structure leaves the catalytic site accessible.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mthfr-allostery-2024] Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase (2024). https://pubmed.ncbi.nlm.nih.gov/38622112/ DOI: 10.1038/s41467-024-47174-y","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified protein","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"a3f13e6b-cd77-5a99-a524-c507d35b8c21","evidence_kind":"source_excerpt","locator":"Lines 471-480","start_line":471,"end_line":480,"excerpt":"### folate-methyl-sah-active-state\nSingle SAH occupancy accompanied a flexible catalytic domain with an exposed active site in human MTHFR structures.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The SAH-bound structure leaves the catalytic site accessible.\norganism: Homo sapiens\ntissue_or_cell_type: Purified protein\nexperimental_model: Recombinant human MTHFR; cryo-EM and biochemistry.\nlimitations: Does not imply SAH promotes all methyltransferases.\n[mthfr-allostery-2024] Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase (2024). https://pubmed.ncbi.nlm.nih.gov/38622112/ DOI: 10.1038/s41467-024-47174-y","model_system":"Recombinant human MTHFR; cryo-EM and biochemistry.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mthfr-allostery-2024] Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase (2024). https://pubmed.ncbi.nlm.nih.gov/38622112/ DOI: 10.1038/s41467-024-47174-y","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: 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":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}