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zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda\", \"start_char\": 0, \"end_char\": 2200, \"text_sha256\": \"773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"D- and L-ibuprofen and flurbiprofen tested against the mutant panel","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Identifies which residue does the stereochemical discrimination by changing it and watching the discrimination collapse. 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(1996). https://pubmed.ncbi.nlm.nih.gov/8567676/ DOI: 10.1074/jbc.271.4.2179","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Recombinant cyclooxygenase-1","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"254f143e-b3ca-522d-9499-978c55ada4e1","evidence_kind":"source_excerpt","locator":"Lines 253-264","start_line":253,"end_line":264,"excerpt":"### ibu-arg120-anchors-the-carboxylate\nAll mutants retained at least part of their activity except R120E which had none, Km values for arachidonic acid were 87 and 3300 micromolar for R120K and R120Q against 4 micromolar for native enzyme, and the R120Q mutant failed to undergo suicide inactivation during catalysis or time-dependent inhibition by flurbiprofen, results consistent with Arg120 binding the carboxylate group of arachidonate and indicating that interaction of the carboxylate of substrates and inhibitors with Arg120 is necessary for suicide inactivation and time-dependent inhibition respectively; Glu524 substitutions did not significantly change Km.\nCondition category: normal\nnutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.\nplain_language: A single arginine grips the acid group of both the substrate and the drug, and without it the slow kind of inhibition cannot happen.\norganism: Sheep enzyme\ntissue_or_cell_type: Recombinant cyclooxygenase-1\nexperimental_model: Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells\nlimitations: Identifies which residue does the stereochemical discrimination by changing it and watching the discrimination collapse. Ovine recombinant enzyme.\nexposure: D- and L-ibuprofen and flurbiprofen tested against the mutant panel\nevidence_span: {\"source_cache\": \"artifacts/ibuprofen-research/8567676.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda\", \"start_char\": 0, \"end_char\": 2200, \"text_sha256\": \"773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda\"}\n[ibu-p8567676] Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1. (1996). https://pubmed.ncbi.nlm.nih.gov/8567676/ DOI: 10.1074/jbc.271.4.2179","model_system":"Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ibu-p8567676] Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1. 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