{"id":"a51d6215-2ddc-5cc0-8acd-f61c6dd233ce","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-arg2-metal-hydroxide","predicate":"supports","statement":"The active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"4902cf3c-4624-59d2-80d1-8edb58fbc557","mechanism_event_label":"Two manganese ions help ARG2 activate the water-derived attacking group.","subject":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"object":{"id":"8ea15e8d-d518-5929-997d-0fa4091785fb","slug":"arg2","display_name":"Human arginase 2 / ARG2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"4902cf3c-4624-59d2-80d1-8edb58fbc557","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-arg2-metal-hydroxide-event","event_type":"biochemical_relationship","label":"Two manganese ions help ARG2 activate the water-derived attacking group.","description":"The active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis.","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":"8ea15e8d-d518-5929-997d-0fa4091785fb","slug":"arg2","display_name":"Human arginase 2 / ARG2","entity_type_key":"protein"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d31225b7-8e94-5857-9ea1-67ac794b1f15","slug":"water","display_name":"H2O","entity_type_key":"small_molecule"},"role":"source of attacking hydroxide","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"eeca3c9e-7749-5677-b7bd-37fe8f7c228d","slug":"arginine","display_name":"L-Arginine","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Crystal structure of active truncated human ARG2 with transition-state analogue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Boronic-acid inhibitor complex; 2.7-A structure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Structural consistency with the proposed mechanism; truncated active recombinant human ARG2 with inhibitor, not direct dietary manganese perturbation.","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":"Two manganese ions help ARG2 activate the water-derived attacking group.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-enz-12859189] Human arginase II: crystal structure and physiological role in male and female sexual arousal. (2003). https://pubmed.ncbi.nlm.nih.gov/12859189/ DOI: 10.1021/bi034340j","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified ARG2","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b7e85d4f-e62a-5cd2-ac3e-323c3a521b1e","evidence_kind":"source_excerpt","locator":"Lines 584-594","start_line":584,"end_line":594,"excerpt":"### mn-enz-arg2-metal-hydroxide\nThe active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Two manganese ions help ARG2 activate the water-derived attacking group.\norganism: Homo sapiens protein\ntissue_or_cell_type: Purified ARG2\nexperimental_model: Crystal structure of active truncated human ARG2 with transition-state analogue\nlimitations: Structural consistency with the proposed mechanism; truncated active recombinant human ARG2 with inhibitor, not direct dietary manganese perturbation.\nexposure: Boronic-acid inhibitor complex; 2.7-A structure\n[mn-enz-12859189] Human arginase II: crystal structure and physiological role in male and female sexual arousal. 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