{"id":"f97d6e27-2781-57c6-a4d5-8075285ebc2a","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cyp2r1-heme","predicate":"binds_cofactor","statement":"The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"f1092c3e-4877-51ba-ac56-29f840571b02","mechanism_event_label":"D3 activation uses an iron-containing heme enzyme.","subject":{"id":"54fd3aae-6183-5f9a-827e-f4dd7683eea7","slug":"cyp2r1","display_name":"Human vitamin D 25-hydroxylase / CYP2R1","entity_type_key":"protein"},"object":{"id":"2e1f7e0a-8b54-5ea3-9d34-01e7167f9097","slug":"heme","display_name":"Heme","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"f1092c3e-4877-51ba-ac56-29f840571b02","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cyp2r1-heme-event","event_type":"biochemical_relationship","label":"D3 activation uses an iron-containing heme enzyme.","description":"The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"54fd3aae-6183-5f9a-827e-f4dd7683eea7","slug":"cyp2r1","display_name":"Human vitamin D 25-hydroxylase / CYP2R1","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2e1f7e0a-8b54-5ea3-9d34-01e7167f9097","slug":"heme","display_name":"Heme","entity_type_key":"small_molecule"},"role":"prosthetic_group","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"heme_element","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b162e431-b442-5400-9335-ec91f7875a4e","slug":"cholecalciferol","display_name":"Cholecalciferol","entity_type_key":"small_molecule"},"role":"bound_substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Primary abstract and structure PDB 3C6G.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human enzyme crystallography","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"CYP2R1-D3 crystal complex; PDB 3C6G.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Vitamin D2 and D3","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"nutrient_topic","value_text":"Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"D3 activation uses an iron-containing heme enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CYP2R1 active site","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4c00d1f6-32a1-5122-aef9-19e5251c25d2","evidence_kind":"source_excerpt","locator":"Lines 377-390","start_line":377,"end_line":390,"excerpt":"### vd-act-cyp2r1-heme\nThe human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group.\nCondition category: normal\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: D3 activation uses an iron-containing heme enzyme.\norganism: Homo sapiens protein\ntissue_or_cell_type: CYP2R1 active site\nexperimental_model: Purified human enzyme crystallography\nlimitations: A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people.\nexposure: CYP2R1-D3 crystal complex; PDB 3C6G.\ncross_nutrient: true\nevidence_location: Primary abstract and structure PDB 3C6G.\nnutrient: Vitamin D2 and D3\n[strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065","model_system":"Purified human enzyme crystallography","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c95c763c-5b31-5b3f-a2f8-2dfe5ef0d3ca","stable_key":"import-1deb434a-3547-51a0-a038-87b1ce79ec38","title":"Vitamin D2 and D3: 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. 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