{"id":"1a59eced-7aeb-5cdc-be62-6e2a9a671741","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-arg1-binuclear-transition-state","predicate":"supports","statement":"Human ARG1 structures show a binuclear manganese site binding a boronate transition-state analogue, supporting metal stabilization of the arginine-hydrolysis transition state.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"89feef2b-c581-570d-ae3e-661d7092bff3","mechanism_event_label":"ARG1 holds two manganese ions at the site where arginine is hydrolyzed.","subject":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","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":"89feef2b-c581-570d-ae3e-661d7092bff3","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-arg1-binuclear-transition-state-event","event_type":"biochemical_relationship","label":"ARG1 holds two manganese ions at the site where arginine is hydrolyzed.","description":"Human ARG1 structures show a binuclear manganese site binding a boronate transition-state analogue, supporting metal stabilization of the arginine-hydrolysis transition state.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","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":"eeca3c9e-7749-5677-b7bd-37fe8f7c228d","slug":"arginine","display_name":"L-Arginine","entity_type_key":"small_molecule"},"role":"substrate whose transition state is modeled","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c715e48e-42db-5fac-b4a4-c1285a68d085","slug":"ornithine","display_name":"L-Ornithine","entity_type_key":"small_molecule"},"role":"hydrolysis product","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"X-ray structures of human ARG1 with boronic-acid transition-state analogues","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"ABH and BEC inhibitor complexes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Transition-state analogue crystallography and author mechanistic inference; not direct nutritional manganese restriction.","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":"ARG1 holds two manganese ions at the site where arginine is hydrolyzed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-enz-16141327] Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. (2005). https://pubmed.ncbi.nlm.nih.gov/16141327/ DOI: 10.1073/pnas.0504027102","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified ARG1","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"33b1cdb8-0d8e-5639-ab70-30293b1365a2","evidence_kind":"source_excerpt","locator":"Lines 534-544","start_line":534,"end_line":544,"excerpt":"### mn-enz-arg1-binuclear-transition-state\nHuman ARG1 structures show a binuclear manganese site binding a boronate transition-state analogue, supporting metal stabilization of the arginine-hydrolysis transition state.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: ARG1 holds two manganese ions at the site where arginine is hydrolyzed.\norganism: Homo sapiens protein\ntissue_or_cell_type: Purified ARG1\nexperimental_model: X-ray structures of human ARG1 with boronic-acid transition-state analogues\nlimitations: Transition-state analogue crystallography and author mechanistic inference; not direct nutritional manganese restriction.\nexposure: ABH and BEC inhibitor complexes\n[mn-enz-16141327] Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. (2005). https://pubmed.ncbi.nlm.nih.gov/16141327/ DOI: 10.1073/pnas.0504027102","model_system":"X-ray structures of human ARG1 with boronic-acid transition-state analogues","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mn-enz-16141327] Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. (2005). https://pubmed.ncbi.nlm.nih.gov/16141327/ DOI: 10.1073/pnas.0504027102","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"03224387-8a73-5b4f-906d-9f0be6625b7f","stable_key":"import-be889add-cec8-500b-be89-676431432a70","title":"Manganese: enzyme cofactors, glycosylation, transport 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. 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