{"id":"5b0507ad-ac05-5beb-b387-fb452c486519","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-h3-activation","predicate":"activates_tested","statement":"Histamine-bound human H3 receptor was resolved with an engineered Gi-family protein complex, with binding and functional mutagenesis supporting ligand recognition and coupling.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"84673c0a-824c-55bd-b598-6ba44ebe157e","mechanism_event_label":"The same histidine-derived messenger can activate a distinct receptor route.","subject":{"id":"847daefd-ce13-541a-b426-919975168a3d","slug":"histamine","display_name":"Histamine","entity_type_key":"small_molecule"},"object":{"id":"baf4988c-72fc-53b6-b24b-20a87f7654e9","slug":"hrh3","display_name":"Human histamine H3 receptor / HRH3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"84673c0a-824c-55bd-b598-6ba44ebe157e","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-h3-activation-event","event_type":"observed_relationship","label":"The same histidine-derived messenger can activate a distinct receptor route.","description":"Histamine-bound human H3 receptor was resolved with an engineered Gi-family protein complex, with binding and functional mutagenesis supporting ligand recognition and coupling.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"847daefd-ce13-541a-b426-919975168a3d","slug":"histamine","display_name":"Histamine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"baf4988c-72fc-53b6-b24b-20a87f7654e9","slug":"hrh3","display_name":"Human histamine H3 receptor / HRH3","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6e02d404-1082-5670-bd1c-66678150b479","slug":"human-hrh3-gi-coupling","display_name":"Human H3 receptor Gi coupling","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Engineered human receptor complexes produced in insect cells, cryo-EM and HEK293 binding/G-protein assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Structural stabilization, chimeric/mini G proteins and recombinant cells differ from native tissues; receptor engagement is not proof that oral histidine produces this response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The same histidine-derived messenger can activate a distinct receptor route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structural basis of ligand recognition and activation of the histamine receptor family. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39333117/ · DOI 10.1038/s41467-024-52585-y","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"69f88f95-e3d2-5f1c-8e63-4e0912c494b6","evidence_kind":"source_excerpt","locator":"Lines 242-248","start_line":242,"end_line":248,"excerpt":"## histidine-h3-activation\nThe same histidine-derived messenger can activate a distinct receptor route.\nHistamine-bound human H3 receptor was resolved with an engineered Gi-family protein complex, with binding and functional mutagenesis supporting ligand recognition and coupling.\nModel: Engineered human receptor complexes produced in insect cells, cryo-EM and HEK293 binding/G-protein assays.\nLimitations: Structural stabilization, chimeric/mini G proteins and recombinant cells differ from native tissues; receptor engagement is not proof that oral histidine produces this response.\nEvidence access: Primary full text\nStructural basis of ligand recognition and activation of the histamine receptor family. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39333117/ · DOI 10.1038/s41467-024-52585-y","model_system":"Engineered human receptor complexes produced in insect cells, cryo-EM and HEK293 binding/G-protein assays.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"cb672530ec8b4a4542d0f3957e80ca76bb0449e9f988845b0f7681f623c4ec9b","revision_id":"19a7f26c-d9a1-5411-a81d-025f3d98a452","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}