{"id":"26a01709-fb05-5f50-8ec8-0c66bb57f701","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-vacht-vesamicol","predicate":"binds_and_inhibits","statement":"The human VAChT structure captured vesamicol in its inhibitory binding site.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ba4f8995-6ca9-548f-9915-a1f2dd531c51","mechanism_event_label":"A drug can interrupt packaging without being a choline shortage.","subject":{"id":"c3443666-13b8-5985-8819-297c9583e42c","slug":"vesamicol","display_name":"Vesamicol","entity_type_key":"small_molecule"},"object":{"id":"a683cdc5-3655-5872-9b3e-bbd454b7bc34","slug":"slc18a3","display_name":"Human vesicular acetylcholine transporter VAChT / SLC18A3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ba4f8995-6ca9-548f-9915-a1f2dd531c51","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-vacht-vesamicol-event","event_type":"biochemical_relationship","label":"A drug can interrupt packaging without being a choline shortage.","description":"The human VAChT structure captured vesamicol in its inhibitory binding site.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c3443666-13b8-5985-8819-297c9583e42c","slug":"vesamicol","display_name":"Vesamicol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a683cdc5-3655-5872-9b3e-bbd454b7bc34","slug":"slc18a3","display_name":"Human vesicular acetylcholine transporter VAChT / SLC18A3","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/choline-research/39806024.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78\", \"start_char\": 0, \"end_char\": 1047, \"text_sha256\": \"e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Acetylcholine and vesamicol ligand binding","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Packaging is distinct from synthesis and release. Structures support substrate recognition and protonation coupling, not a clinical effect of choline supplementation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Choline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human VAChT protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A drug can interrupt packaging without being a choline shortage.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[choline-p39806024] Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT. (2025). https://pubmed.ncbi.nlm.nih.gov/39806024/ DOI: 10.1038/s41594-024-01462-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Synaptic-vesicle transporter","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"101715b4-a462-5357-8e1d-d0af9f200a73","evidence_kind":"source_excerpt","locator":"Lines 451-462","start_line":451,"end_line":462,"excerpt":"### choline-vacht-vesamicol\nThe human VAChT structure captured vesamicol in its inhibitory binding site.\nCondition category: normal\nnutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A drug can interrupt packaging without being a choline shortage.\norganism: Human VAChT protein\ntissue_or_cell_type: Synaptic-vesicle transporter\nexperimental_model: Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states\nlimitations: Packaging is distinct from synthesis and release. Structures support substrate recognition and protonation coupling, not a clinical effect of choline supplementation.\nexposure: Acetylcholine and vesamicol ligand binding\nevidence_span: {\"source_cache\": \"artifacts/choline-research/39806024.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78\", \"start_char\": 0, \"end_char\": 1047, \"text_sha256\": \"e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78\"}\n[choline-p39806024] Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT. (2025). https://pubmed.ncbi.nlm.nih.gov/39806024/ DOI: 10.1038/s41594-024-01462-9","model_system":"Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [choline-p39806024] Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT. (2025). https://pubmed.ncbi.nlm.nih.gov/39806024/ DOI: 10.1038/s41594-024-01462-9","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0ba2f05e-5cf5-5bd7-ae5d-0ab4945fcb7b","stable_key":"import-27e0c1cf-7726-5164-8b15-27a631584cd0","title":"Choline: metabolism, signaling and nutrient connections (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":"c7afe3d579eba0df6d2a4c26699c653462749e03188348f900c07748cc7282a8","revision_id":"0fa7b48f-2a3c-5adc-b13e-48727dd6f815","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}