Component
Residues Val-434, Arg-513 and Val-523 that distinguish the two cyclooxygenase active sites
Residues Val-434, Arg-513 and Val-523 that distinguish the two cyclooxygenase active sites. Species, exposure and limitations are retained in each linked claim.
1 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What it acts on
Acetylated cyclooxygenase-2 is essentially a lipoxygenase making 15(R)- and 11(R)-hydroxyeicosatetraenoic acid whereas acetylated cyclooxygenase-1 is unable to oxidise arachidonic acid to any products, and site-directed mutagenesis of Val-434, Arg-513 and Val-523 in mouse cyclooxygenase-2 to their cyclooxygenase-1 equivalents abrogated 11- and 15-HETE production after aspirin treatment, confirming these residues as the major isoform selectivity determinants; V228F and G533A produced wild-type-like profiles but on acetylation neither could make HETE products, suggesting arachidonic acid orientates in an L-shaped binding configuration.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/aspirin-research/10692466.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da1ede1fbf95d6f42d4bb15dc08b5d1869549a7cd94cbfa9da9f9865fd780ff", "start_char": 0, "end_char": 2055, "text_sha256": "9da1ede1fbf95d6f42d4bb15dc08b5d1869549a7cd94cbfa9da9f9865fd780ff"}
- experimental_model
- Site-directed mutagenesis of mouse COX-2 residues predicted from comparison of the two isoform crystal structures
- exposure
- Val-434, Arg-513, Val-523, Val-228 and Gly-533 mutated towards their cyclooxygenase-1 equivalents, then acetylated
- limitations
- Explains the isoform difference residue by residue. Murine enzyme, and the L-shaped substrate configuration is an inference from the mutant product profiles.
- nutrient_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. · Aspirin / acetylsalicylic acid
- organism
- Mouse enzyme
- plain_language
- Three amino acids are the whole difference between an enzyme aspirin kills and one aspirin repurposes.
- primary_references
- [asa-p10692466] Spatial requirements for 15-(R)-hydroxy-5Z,8Z,11Z, 13E-eicosatetraenoic acid synthesis within the cyclooxygenase active site of murine COX-2. Why acetylated COX-1 does not synthesize 15-(R)-hete. (2000). https://pubmed.ncbi.nlm.nih.gov/10692466/ DOI: 10.1074/jbc.275.9.6586
- tissue_or_cell_type
- Cyclooxygenase-2
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis of mouse COX-2 residues predicted from comparison of the two isoform crystal structures · source_derived_draft · unverified_draft
### asa-three-residues-decide Acetylated cyclooxygenase-2 is essentially a lipoxygenase making 15(R)- and 11(R)-hydroxyeicosatetraenoic acid whereas acetylated cyclooxygenase-1 is unable to oxidise arachidonic acid to any products, and site-directed mutagenesis of Val-434, Arg-513 and Val-523 in mouse cyclooxygenase-2 to their cyclooxygenase-1 equivalents abrogated 11- and 15-HETE production after aspirin treatment, confirming these residues as the major isoform selectivity determinants; V228F and G533A produced wild-type-like profiles but on acetylation neither could make HETE products, suggesting arachidonic acid orientates in an L-shaped binding configuration. Condition category: normal nutrient_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. plain_language: Three amino acids are the whole difference between an enzyme aspirin kills and one aspirin repurposes. organism: Mouse enzyme tissue_or_cell_type: Cyclooxygenase-2 experimental_model: Site-directed mutagenesis of mouse COX-2 residues predicted from comparison of the two isoform crystal structures limitations: Explains the isoform difference residue by residue. Murine enzyme, and the L-shaped substrate configuration is an inference from the mutant product profiles. exposure: Val-434, Arg-513, Val-523, Val-228 and Gly-533 mutated towards their cyclooxygenase-1 equivalents, then acetylated evidence_span: {"source_cache": "artifacts/aspirin-research/10692466.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da1ede1fbf95d6f42d4bb15dc08b5d1869549a7cd94cbfa9da9f9865fd780ff", "start_char": 0, "end_char": 2055, "text_sha256": "9da1ede1fbf95d6f42d4bb15dc08b5d1869549a7cd94cbfa9da9f9865fd780ff"} [asa-p10692466] Spatial requirements for 15-(R)-hydroxy-5Z,8Z,11Z, 13E-eicosatetraenoic acid synthesis within the cyclooxygenase active site of murine COX-2. Why acetylated COX-1 does not synthesize 15-(R)-hete. (2000). https://pubmed.ncbi.nlm.nih.gov/10692466/ DOI: 10.1074/jbc.275.9.6586
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.