{"id":"f16fff71-66cc-570d-93e8-b6855593c547","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-arg1-zinc-inhibition","predicate":"inhibits","statement":"Added Zn(II) bound the H141/E277 region of manganese-loaded human ARG1, revealing a structural basis for zinc inhibition.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ceb8f636-0b25-5a08-87df-be6a02f3d974","mechanism_event_label":"Zinc can inhibit purified manganese-loaded ARG1 at an additional site.","subject":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"object":{"id":"9ea9b9b8-13b7-585e-a17e-5bd708742e29","slug":"arg1","display_name":"Human arginase 1 / ARG1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ceb8f636-0b25-5a08-87df-be6a02f3d974","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-arg1-zinc-inhibition-event","event_type":"biochemical_relationship","label":"Zinc can inhibit purified manganese-loaded ARG1 at an additional site.","description":"Added Zn(II) bound the H141/E277 region of manganese-loaded human ARG1, revealing a structural basis for zinc inhibition.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9ea9b9b8-13b7-585e-a17e-5bd708742e29","slug":"arg1","display_name":"Human arginase 1 / ARG1","entity_type_key":"protein"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"role":"native binuclear cofactor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Zn inhibition of a Mn enzyme was structurally measured in purified protein; no dietary threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Metal-substitution crystallography and kinetics of purified human ARG1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Non-native metal reconstitution or added zinc","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Zinc can inhibit purified manganese-loaded ARG1 at an additional site.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-enz-23061982] Structure and function of non-native metal clusters in human arginase I. (2012). https://pubmed.ncbi.nlm.nih.gov/23061982/ DOI: 10.1021/bi301145n","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified enzyme","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"cc9c005e-cf43-57bd-a051-c9af2456b0bf","evidence_kind":"source_excerpt","locator":"Lines 559-570","start_line":559,"end_line":570,"excerpt":"### mn-enz-arg1-zinc-inhibition\nAdded Zn(II) bound the H141/E277 region of manganese-loaded human ARG1, revealing a structural basis for zinc inhibition.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Zinc can inhibit purified manganese-loaded ARG1 at an additional site.\norganism: Homo sapiens protein\ntissue_or_cell_type: Purified enzyme\nexperimental_model: Metal-substitution crystallography and kinetics of purified human ARG1\nlimitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.\nexposure: Non-native metal reconstitution or added zinc\ncross_nutrient: Zn inhibition of a Mn enzyme was structurally measured in purified protein; no dietary threshold.\n[mn-enz-23061982] Structure and function of non-native metal clusters in human arginase I. 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