{"id":"01197b30-643d-53d8-98d2-b3e39653b0fc","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-tg-acceptor-mutants","predicate":"abolishes","statement":"Replacing human TG acceptors Y24, Y2573, Y2766 and Y1310 with phenylalanine eliminated detectable T4 formation in the reconstituted assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"67407c2c-b4c4-5aa7-95a5-48c3fe91f6d6","mechanism_event_label":"Four hormone-forming acceptor sites account for the measured T4 production.","subject":{"id":"5ef97b7d-5ded-5037-a1ab-ce5adecc4395","slug":"human-tg-four-acceptor-yf","display_name":"Human TG four-acceptor Y-to-F mutant","entity_type_key":"protein_state"},"object":{"id":"724d042c-df5d-55ed-8066-61131da0e888","slug":"tg-derived-t4-production","display_name":"Tg derived t4 production","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"67407c2c-b4c4-5aa7-95a5-48c3fe91f6d6","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-tg-acceptor-mutants-event","event_type":"biochemical_relationship","label":"Four hormone-forming acceptor sites account for the measured T4 production.","description":"Replacing human TG acceptors Y24, Y2573, Y2766 and Y1310 with phenylalanine eliminated detectable T4 formation in the reconstituted assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ab42f761-f2c0-52e6-876b-12df0d1d03d7","slug":"thyroglobulin","display_name":"Human thyroglobulin","entity_type_key":"protein"},"role":"wild_type_control","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"83b11ca6-52c7-5a1b-8c39-d9cdf89244e3","slug":"iodide","display_name":"Iodide ion","entity_type_key":"ion"},"role":"iodination_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f2b25f38-ec94-57d0-a46d-dd0fee45f01e","slug":"thyroxine","display_name":"T4","entity_type_key":"small_molecule"},"role":"measured_product","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5ef97b7d-5ded-5037-a1ab-ce5adecc4395","slug":"human-tg-four-acceptor-yf","display_name":"Human TG four-acceptor Y-to-F mutant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"724d042c-df5d-55ed-8066-61131da0e888","slug":"tg-derived-t4-production","display_name":"Tg derived t4 production","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iodine-synthesis-sources/32025030.txt\", \"start_char\": 8677, \"end_char\": 9897, \"text_sha256\": \"fcdc18c2b096fdd24073329828fe9c6681e101b7f29bf985938e538faf6fb3fe\", \"text_characters\": 1220, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Four acceptor substitutions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered multi-site mutant; no human congenital phenotype inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens TG","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Four hormone-forming acceptor sites account for the measured T4 production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified-protein reaction","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c4d87497-ea0d-52eb-986a-593460423d54","evidence_kind":"source_excerpt","locator":"Lines 632-644","start_line":632,"end_line":644,"excerpt":"### iodine-syn-tg-acceptor-mutants\nReplacing human TG acceptors Y24, Y2573, Y2766 and Y1310 with phenylalanine eliminated detectable T4 formation in the reconstituted assay.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Four hormone-forming acceptor sites account for the measured T4 production.\norganism: Homo sapiens TG\ntissue_or_cell_type: Purified-protein reaction\nexperimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants\nlimitations: Engineered multi-site mutant; no human congenital phenotype inferred.\nexposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Four acceptor substitutions.\ncross_nutrient: false\nevidence_span: {\"source_cache\": \"artifacts/iodine-synthesis-sources/32025030.txt\", \"start_char\": 8677, \"end_char\": 9897, \"text_sha256\": \"fcdc18c2b096fdd24073329828fe9c6681e101b7f29bf985938e538faf6fb3fe\", \"text_characters\": 1220, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}\n[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4","model_system":"Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"76da623d-a34a-5a5c-a942-d7571a85c486","stable_key":"import-aaa7baba-8689-56ab-ba1e-b71542bcb8e9","title":"Iodine: thyroid hormone production, deficiency, excess 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":"a4885eb6f58bad4a4514c958b63834619e57b10aa7f694aa97d0f65c7d36548f","revision_id":"ea8001a1-b576-5eda-a193-883c7ad59b73","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}