{"id":"2b8c3edb-ffbb-543e-97d3-bb3710c0d113","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-sarm-nad-binding","predicate":"competes_with_nmn_at","statement":"NAD+ bound the same Drosophila SARM1 ARM-domain regulatory site with approximately 54.2 micromolar dissociation constant; competition assays supported opposing occupancy by NAD+ and NMN.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f5d367d7-9556-539c-87a7-67698c65e122","mechanism_event_label":"NAD can help restrain the switch at a regulatory site while also being its substrate.","subject":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"object":{"id":"a0a579c6-f601-5fbe-bf0e-d72a440dfbb1","slug":"drosophila-sarm1-arm-307-678","display_name":"Drosophila SARM1 ARM domain residues 307–678","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"f5d367d7-9556-539c-87a7-67698c65e122","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-sarm-nad-binding-event","event_type":"observed_relationship","label":"NAD can help restrain the switch at a regulatory site while also being its substrate.","description":"NAD+ bound the same Drosophila SARM1 ARM-domain regulatory site with approximately 54.2 micromolar dissociation constant; competition assays supported opposing occupancy by NAD+ and NMN.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a0a579c6-f601-5fbe-bf0e-d72a440dfbb1","slug":"drosophila-sarm1-arm-307-678","display_name":"Drosophila SARM1 ARM domain residues 307–678","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d1c59139-db61-5fa0-a25d-40c3e625152e","slug":"nmn","display_name":"NMN","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Drosophila-domain ITC and NMR competition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Species/domain-specific affinity; separate from catalytic-site kinetics.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"NAD can help restrain the switch at a regulatory site while also being its substrate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9ed2efd3-9e71-554e-9320-3f8e40f0fb5e","evidence_kind":"source_excerpt","locator":"Lines 92-98","start_line":92,"end_line":98,"excerpt":"## nad-plus-sarm-nad-binding\nNAD can help restrain the switch at a regulatory site while also being its substrate.\nNAD+ bound the same Drosophila SARM1 ARM-domain regulatory site with approximately 54.2 micromolar dissociation constant; competition assays supported opposing occupancy by NAD+ and NMN.\nModel: Drosophila-domain ITC and NMR competition.\nLimitations: Species/domain-specific affinity; separate from catalytic-site kinetics.\nEvidence access: Primary full text\nSARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009","model_system":"Drosophila-domain ITC and NMR competition.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f59aa302-d463-5462-876f-e21e64861eac","stable_key":"import-8c946991-97f0-55ee-8df0-00e67621962f","title":"NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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