{"id":"dec44408-95de-5a9b-991a-b07f85deec47","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-acetylates-other-enzymes","predicate":"acetylates","statement":"Aspirin causes time-dependent inhibition and acetylation of plant allene oxide synthase leading to irreversible inactivation of this cytochrome P450, acetylating three serine residues near the C-terminal region that are highly conserved among allene oxide synthases but not among classical P450s; unlike animal cyclooxygenase, where acetylation of a single serine within the substrate channel causes inactivation, these three serines are not thought to line the putative substrate channel, so inhibition may be by a different mechanism, and aspirin could inhibit other P450s with similar motifs.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c4eee317-f7b4-5bbc-9ce7-14db5fc00e5f","mechanism_event_label":"Aspirin hands its acetyl group to other enzymes too, including one in plants, and not always at the substrate channel.","subject":{"id":"8ac405bf-3ea0-539a-8e5e-abf503dc7081","slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"},"object":{"id":"5dbfb765-dd34-5314-a1ca-49275003baf0","slug":"allene-oxide-synthase","display_name":"Plant allene oxide synthase, a cytochrome P450","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"c4eee317-f7b4-5bbc-9ce7-14db5fc00e5f","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-acetylates-other-enzymes-event","event_type":"biochemical_relationship","label":"Aspirin hands its acetyl group to other enzymes too, including one in plants, and not always at the substrate channel.","description":"Aspirin causes time-dependent inhibition and acetylation of plant allene oxide synthase leading to irreversible inactivation of this cytochrome P450, acetylating three serine residues near the C-terminal region that are highly conserved among allene oxide synthases but not among classical P450s; unlike animal cyclooxygenase, where acetylation of a single serine within the substrate channel causes inactivation, these three serines are not thought to line the putative substrate channel, so inhibition may be by a different mechanism, and aspirin could inhibit other P450s with similar motifs.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0b90732d-d592-5de4-8507-a34b19665086","slug":"jasmonate-synthesis","display_name":"Synthesis of 12-oxo-phytodienoic acid and jasmonates in plants","entity_type_key":"cellular_process"},"role":"blocked_pathway","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5739797a-3699-591b-95fd-f8b80e612713","slug":"salicylate","display_name":"Salicylate / salicylic acid","entity_type_key":"small_molecule"},"role":"co_tested_compound","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8ac405bf-3ea0-539a-8e5e-abf503dc7081","slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5dbfb765-dd34-5314-a1ca-49275003baf0","slug":"allene-oxide-synthase","display_name":"Plant allene oxide synthase, a cytochrome P450","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/aspirin-research/9660772.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259\", \"start_char\": 0, \"end_char\": 1662, \"text_sha256\": \"49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Inhibition and acetylation of plant allene oxide synthase, a cytochrome P450","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Aspirin and salicylic acid applied to the plant oxylipin pathway","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Recorded because it shows the acetyl group is not specific to cyclooxygenase. The three acetylated serines here are not thought to line the substrate channel, so the mechanism may differ from the one at cyclooxygenase.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.","comparator":null,"unit":null,"notes":"","entity":{"slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Plant","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Aspirin hands its acetyl group to other enzymes too, including one in plants, and not always at the substrate channel.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[asa-p9660772] Aspirin inhibition and acetylation of the plant cytochrome P450, allene oxide synthase, resembles that of animal prostaglandin endoperoxide H synthase. (1998). https://pubmed.ncbi.nlm.nih.gov/9660772/ DOI: 10.1074/jbc.273.29.18139","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Allene oxide synthase","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7350a7da-47e5-5d73-8cdf-569d9acd46de","evidence_kind":"source_excerpt","locator":"Lines 195-206","start_line":195,"end_line":206,"excerpt":"### asa-acetylates-other-enzymes\nAspirin causes time-dependent inhibition and acetylation of plant allene oxide synthase leading to irreversible inactivation of this cytochrome P450, acetylating three serine residues near the C-terminal region that are highly conserved among allene oxide synthases but not among classical P450s; unlike animal cyclooxygenase, where acetylation of a single serine within the substrate channel causes inactivation, these three serines are not thought to line the putative substrate channel, so inhibition may be by a different mechanism, and aspirin could inhibit other P450s with similar motifs.\nCondition category: normal\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: Aspirin hands its acetyl group to other enzymes too, including one in plants, and not always at the substrate channel.\norganism: Plant\ntissue_or_cell_type: Allene oxide synthase\nexperimental_model: Inhibition and acetylation of plant allene oxide synthase, a cytochrome P450\nlimitations: Recorded because it shows the acetyl group is not specific to cyclooxygenase. The three acetylated serines here are not thought to line the substrate channel, so the mechanism may differ from the one at cyclooxygenase.\nexposure: Aspirin and salicylic acid applied to the plant oxylipin pathway\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/9660772.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259\", \"start_char\": 0, \"end_char\": 1662, \"text_sha256\": \"49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259\"}\n[asa-p9660772] Aspirin inhibition and acetylation of the plant cytochrome P450, allene oxide synthase, resembles that of animal prostaglandin endoperoxide H synthase. 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