{"id":"0963435f-22c2-5e4d-8c97-7d60c70acac6","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-trans-shared-substrate-site","predicate":"binds_at_shared_site","statement":"Human SMVT cryo-EM complexes placed pantothenate, biotin and oxidized lipoate in substantially overlapping positions within one central substrate-binding pocket.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"f6b445f6-b71c-534b-9d33-fad97c6b74aa","mechanism_event_label":"B5, biotin and free lipoate use the same binding pocket in SMVT.","subject":{"id":"3bd59e38-e6b1-5223-b4de-faa33835f5bc","slug":"slc5a6","display_name":"Human sodium-dependent multivitamin transporter / SLC5A6","entity_type_key":"protein"},"object":{"id":"7bc62072-9517-5563-a3b8-8c5ab64a464b","slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"f6b445f6-b71c-534b-9d33-fad97c6b74aa","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-trans-shared-substrate-site-event","event_type":"biochemical_relationship","label":"B5, biotin and free lipoate use the same binding pocket in SMVT.","description":"Human SMVT cryo-EM complexes placed pantothenate, biotin and oxidized lipoate in substantially overlapping positions within one central substrate-binding pocket.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7bc62072-9517-5563-a3b8-8c5ab64a464b","slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"},"role":"alternative_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"alternative_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"role":"alternative_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":"Free oxidized alpha-lipoic acid; not a protein-bound lipoyl group."},{"entity":{"id":"3bd59e38-e6b1-5223-b4de-faa33835f5bc","slug":"slc5a6","display_name":"Human sodium-dependent multivitamin transporter / SLC5A6","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SMVTEM/NbALFA complexes incubated with 2 mM D-pantothenic acid, 4 mM biotin or 22 mM oxidized alpha-lipoic acid for separate structures.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. These are separate ligand-bound complexes, not simultaneous occupancy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"B5, biotin and free lipoate use the same binding pocket in SMVT.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified human SMVT; HEK293-derived expression system","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ba70c863-1eab-5679-9cd6-5ba18123c1ff","evidence_kind":"source_excerpt","locator":"Lines 405-416","start_line":405,"end_line":416,"excerpt":"### b5-trans-shared-substrate-site\nHuman SMVT cryo-EM complexes placed pantothenate, biotin and oxidized lipoate in substantially overlapping positions within one central substrate-binding pocket.\nCondition category: normal\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: B5, biotin and free lipoate use the same binding pocket in SMVT.\norganism: Homo sapiens\ntissue_or_cell_type: Purified human SMVT; HEK293-derived expression system\nexperimental_model: Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells\nlimitations: Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. These are separate ligand-bound complexes, not simultaneous occupancy.\nexposure: SMVTEM/NbALFA complexes incubated with 2 mM D-pantothenic acid, 4 mM biotin or 22 mM oxidized alpha-lipoic acid for separate structures.\ncross_nutrient: true\n[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3","model_system":"Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0716b500-dd0b-5425-b9d0-d88bc9c09e86","stable_key":"import-f992b796-377d-53bf-a39b-7e5d41dbe194","title":"Pantothenic acid (vitamin B5): coenzyme A, 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":"b5a49f5a2373ca6064c9a4e014e052dad2f6f199a82bb09b26b82b831c36110b","revision_id":"78f3e793-f084-5ee2-8703-b661c4b650bf","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}