{"id":"62516bb4-3a0e-579e-af32-3d7b33493697","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pah-allostery","predicate":"stabilizes_regulatory_dimer_of","statement":"Phenylalanine bound at the interface of two ACT regulatory domains and stabilized the human PAH regulatory-domain dimer.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"b3c31ed3-8e98-523a-bd0f-2f0d8e73afdd","mechanism_event_label":"Phenylalanine helps switch on the machinery that processes it.","subject":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"object":{"id":"ea908671-6f85-5342-abe4-1a466a3b0572","slug":"pah","display_name":"Human phenylalanine hydroxylase / PAH","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"b3c31ed3-8e98-523a-bd0f-2f0d8e73afdd","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pah-allostery-event","event_type":"observed_relationship","label":"Phenylalanine helps switch on the machinery that processes it.","description":"Phenylalanine bound at the interface of two ACT regulatory domains and stabilized the human PAH regulatory-domain dimer.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ea908671-6f85-5342-abe4-1a466a3b0572","slug":"pah","display_name":"Human phenylalanine hydroxylase / PAH","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Isolated human PAH regulatory domain; 1.8-angstrom crystal structure and biophysical assays; crystallization used 10 mM phenylalanine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An isolated domain at experimental concentrations does not establish an oral-dose activation threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Phenylalanine helps switch on the machinery that processes it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9577def9-6b1b-5a31-b18c-4c98c5aba696","evidence_kind":"source_excerpt","locator":"Lines 22-28","start_line":22,"end_line":28,"excerpt":"## l-phenylalanine-pah-allostery\nPhenylalanine helps switch on the machinery that processes it.\nPhenylalanine bound at the interface of two ACT regulatory domains and stabilized the human PAH regulatory-domain dimer.\nModel: Isolated human PAH regulatory domain; 1.8-angstrom crystal structure and biophysical assays; crystallization used 10 mM phenylalanine.\nLimitations: An isolated domain at experimental concentrations does not establish an oral-dose activation threshold.\nEvidence access: Primary full text\nStructural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748","model_system":"Isolated human PAH regulatory domain; 1.8-angstrom crystal structure and biophysical assays; crystallization used 10 mM phenylalanine.","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":"54de7c56-1e60-5d7b-8ef9-852c58ae92ba","stable_key":"import-56f1d914-e7da-595a-af69-c217b2b47407","title":"L-Phenylalanine: transport, protein synthesis, cofactor recycling 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. 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