{"id":"532c39a5-d57c-5088-91c5-a5c47e8b29b5","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-inos-zinc-interface","predicate":"stabilizes","statement":"The NOS2 zinc-tetrathiolate center supported intersubunit contacts and integrity of the BH4-binding site.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"aea2f6ab-48b6-5a56-a53e-07838f3c0d3c","mechanism_event_label":"The structural metal and the pterin-binding region are connected.","subject":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"object":{"id":"d93fd3a5-ed17-5ca3-a332-4cb1c43007eb","slug":"human-inos-dimer-stability","display_name":"Human iNOS dimer stability","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"aea2f6ab-48b6-5a56-a53e-07838f3c0d3c","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-inos-zinc-interface-event","event_type":"biochemical_relationship","label":"The structural metal and the pterin-binding region are connected.","description":"The NOS2 zinc-tetrathiolate center supported intersubunit contacts and integrity of the BH4-binding site.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"01eede7f-e9e5-556b-b4ec-2ff36d5cca83","slug":"nos2","display_name":"Human inducible nitric oxide synthase / iNOS / NOS2","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1c231b90-c106-507a-8766-870ecb40e368","slug":"tetrahydrobiopterin","display_name":"Tetrahydrobiopterin / BH4","entity_type_key":"small_molecule"},"role":"cofactor_site","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"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":2,"notes":""},{"entity":{"id":"d93fd3a5-ed17-5ca3-a332-4cb1c43007eb","slug":"human-inos-dimer-stability","display_name":"Human iNOS dimer stability","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/citrulline-research/10409685.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c320fb6f3fd659a2e7df4a8ddd3467a902a07b84380075d429040eaf244ccf6b\", \"start_char\": 0, \"end_char\": 942, \"text_sha256\": \"c320fb6f3fd659a2e7df4a8ddd3467a902a07b84380075d429040eaf244ccf6b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Crystal structures of zinc-free and zinc-bound heme domains","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Zinc-free versus zinc-tetrathiolate-containing structures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Direct structure is NOS2; similarity to NOS3 does not justify silently treating the proteins as identical.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Citrulline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human NOS2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The structural metal and the pterin-binding region are connected.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[citrulline-p10409685] Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. (1999). https://pubmed.ncbi.nlm.nih.gov/10409685/ DOI: 10.1074/jbc.274.30.21276","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"NOS dimer interface and pterin-binding region","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c065147c-712a-5e25-81a5-3ec8d151374c","evidence_kind":"source_excerpt","locator":"Lines 606-617","start_line":606,"end_line":617,"excerpt":"### citrulline-inos-zinc-interface\nThe NOS2 zinc-tetrathiolate center supported intersubunit contacts and integrity of the BH4-binding site.\nCondition category: normal\nnutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The structural metal and the pterin-binding region are connected.\norganism: Human NOS2\ntissue_or_cell_type: NOS dimer interface and pterin-binding region\nexperimental_model: Crystal structures of zinc-free and zinc-bound heme domains\nlimitations: Direct structure is NOS2; similarity to NOS3 does not justify silently treating the proteins as identical.\nexposure: Zinc-free versus zinc-tetrathiolate-containing structures\nevidence_span: {\"source_cache\": \"artifacts/citrulline-research/10409685.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c320fb6f3fd659a2e7df4a8ddd3467a902a07b84380075d429040eaf244ccf6b\", \"start_char\": 0, \"end_char\": 942, \"text_sha256\": \"c320fb6f3fd659a2e7df4a8ddd3467a902a07b84380075d429040eaf244ccf6b\"}\n[citrulline-p10409685] Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. (1999). https://pubmed.ncbi.nlm.nih.gov/10409685/ DOI: 10.1074/jbc.274.30.21276","model_system":"Crystal structures of zinc-free and zinc-bound heme domains","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [citrulline-p10409685] Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. (1999). https://pubmed.ncbi.nlm.nih.gov/10409685/ DOI: 10.1074/jbc.274.30.21276","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"112fd375-aa2a-59d2-8afd-6b2849bb79ee","stable_key":"import-a9828b14-fbd7-57bf-9e01-0d52d1b42a1f","title":"Citrulline: arginine recycling, nitrogen disposal and nutrient connections (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":"3720442dbabc28cacefd2145c7c97bfb937df26dca8527fde219ecd3735ed558","revision_id":"41ac8493-b004-59d7-99b3-8a3ca7163d3a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}