{"id":"b50d58b8-e635-5e05-854f-c5fa31556acb","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-iyd-cofactor-substitution","predicate":"reduces","statement":"Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"61cdc1ad-75d3-5818-addf-fba979443c19","mechanism_event_label":"A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster.","subject":{"id":"1db5e1a9-92aa-5e1c-b5cd-0917e586e0a6","slug":"two-prime-deoxy-fmn","display_name":"2-prime-Deoxy-FMN","entity_type_key":"small_molecule"},"object":{"id":"b90d0668-30c8-5ee6-b213-2f5c2fbbd912","slug":"iyd-catalytic-efficiency","display_name":"Iyd catalytic efficiency","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"61cdc1ad-75d3-5818-addf-fba979443c19","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-iyd-cofactor-substitution-event","event_type":"biochemical_relationship","label":"A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster.","description":"Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"50a4f425-207d-55ec-b73e-3e93e7c2695e","slug":"iyd","display_name":"Human iodotyrosine deiodinase","entity_type_key":"protein"},"role":"experimental_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d3eacf85-1a35-546d-bd30-161474dd9691","slug":"fmn","display_name":"Flavin mononucleotide","entity_type_key":"small_molecule"},"role":"native_cofactor_control","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c88508eb-a2ea-56bb-9e69-48fde635fb7f","slug":"monoiodotyrosine","display_name":"3-Iodo-L-tyrosine","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"86eb1eee-a8d1-539c-8c17-0911f69b6f1b","slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"},"role":"native_cofactor_precursor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"1db5e1a9-92aa-5e1c-b5cd-0917e586e0a6","slug":"two-prime-deoxy-fmn","display_name":"2-prime-Deoxy-FMN","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"b90d0668-30c8-5ee6-b213-2f5c2fbbd912","slug":"iyd-catalytic-efficiency","display_name":"Iyd catalytic efficiency","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iodine-synthesis-sources/37654510.txt\", \"start_char\": 9069, \"end_char\": 10489, \"text_sha256\": \"5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1\", \"text_characters\": 1420, \"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":"Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Synthetic cofactor substitution is not riboflavin deficiency; kcat/Km and kcat are different measurements. Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons.","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 recombinant protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. 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Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons.\nexposure: Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1.\ncross_nutrient: true\nevidence_span: {\"source_cache\": \"artifacts/iodine-synthesis-sources/37654510.txt\", \"start_char\": 9069, \"end_char\": 10489, \"text_sha256\": \"5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1\", \"text_characters\": 1420, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}\n[iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. 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