{"id":"3ef5a04e-3638-58c9-a2b7-c0da710f5777","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-eprs-inhibition","predicate":"competitively_inhibits","statement":"Halofuginone inhibited the prolyl-tRNA synthetase activity of EPRS by competing with proline; added proline or enzyme reversed inhibition in the tested systems.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e727ceea-8686-5473-b157-45dab185e590","mechanism_event_label":"Blocking the loading enzyme can mimic a shortage even while proline is present.","subject":{"id":"65134803-3a5b-59ed-a593-5cea114ab988","slug":"halofuginone","display_name":"Halofuginone","entity_type_key":"drug"},"object":{"id":"a0af759a-af37-5303-a1de-f90380b527c0","slug":"eprs1","display_name":"Human glutamyl-prolyl-tRNA synthetase / EPRS1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"e727ceea-8686-5473-b157-45dab185e590","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-eprs-inhibition-event","event_type":"observed_relationship","label":"Blocking the loading enzyme can mimic a shortage even while proline is present.","description":"Halofuginone inhibited the prolyl-tRNA synthetase activity of EPRS by competing with proline; added proline or enzyme reversed inhibition in the tested systems.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"65134803-3a5b-59ed-a593-5cea114ab988","slug":"halofuginone","display_name":"Halofuginone","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a0af759a-af37-5303-a1de-f90380b527c0","slug":"eprs1","display_name":"Human glutamyl-prolyl-tRNA synthetase / EPRS1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Biochemical charging assays and mammalian-cell experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is pharmacological machinery inhibition, not a claim that halofuginone physically removes all cellular proline.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Blocking the loading enzyme can mimic a shortage even while proline is present.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22327401/ · DOI 10.1038/nchembio.790","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"76072414-5dd0-5518-ba84-7cc7f11fff1a","evidence_kind":"source_excerpt","locator":"Lines 230-236","start_line":230,"end_line":236,"excerpt":"## l-proline-eprs-inhibition\nBlocking the loading enzyme can mimic a shortage even while proline is present.\nHalofuginone inhibited the prolyl-tRNA synthetase activity of EPRS by competing with proline; added proline or enzyme reversed inhibition in the tested systems.\nModel: Biochemical charging assays and mammalian-cell experiments.\nLimitations: This is pharmacological machinery inhibition, not a claim that halofuginone physically removes all cellular proline.\nEvidence access: Primary full text\nHalofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22327401/ · DOI 10.1038/nchembio.790","model_system":"Biochemical charging assays and mammalian-cell experiments.","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":"e5aa7fc5-ee52-5376-8169-416082a89fd1","stable_key":"import-6612c190-1948-5bcf-bbe3-a7f6c50fa3cf","title":"L-Proline: synthesis, collagen processing, redox metabolism 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":"7b7f1981f9c7897fbb6baa19425bdc19dede78ad4d66fa554394b8337c7366fb","revision_id":"4971a925-fa70-59f8-8030-d3029a18a62f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}