Component

Cyclooxygenase-1 with alanine substituted at position 530

Cyclooxygenase-1 with alanine substituted at position 530. Species, exposure and limitations are retained in each linked claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

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.

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.

Recorded relationships

What it acts on

  1. Cos-1 cells transfected with native or Ser-530-to-alanine mutant sheep prostaglandin endoperoxide synthase expressed comparable cyclooxygenase and hydroperoxidase activities, with the same Km for arachidonate of 8 micromolar and the same ID50 values for reversible inhibition by flurbiprofen at 5 micromolar, flufenamate at 20 micromolar and aspirin at 20 millimolar; however only the native enzyme was irreversibly inactivated by aspirin, so the active site Ser-530 is not essential for catalysis or substrate binding.

    Cyclooxygenase-1 with alanine substituted at position 530 → The cyclooxygenase activity of prostaglandin endoperoxide synthase source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/2108169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50", "start_char": 0, "end_char": 2076, "text_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50"}
    experimental_model
    Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells
    exposure
    Serine 530 replaced with alanine, compared with the native enzyme against aspirin and reversible inhibitors
    limitations
    The decisive experiment for the mechanism: it separates what the serine does for catalysis from what acetylating it does. Recombinant sheep enzyme, not human enzyme in a tissue.
    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
    Sheep and mouse enzyme
    plain_language
    Remove the serine and the enzyme still works; it is there to be acetylated, not to do the chemistry.
    primary_references
    [asa-p2108169] The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2108169/ DOI: 10.1016/s0021-9258(19)34105-5
    tissue_or_cell_type
    Recombinant enzyme in Cos-1 cells

    Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 78–89

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells · source_derived_draft · unverified_draft

    ### asa-serine-is-not-catalytic Cos-1 cells transfected with native or Ser-530-to-alanine mutant sheep prostaglandin endoperoxide synthase expressed comparable cyclooxygenase and hydroperoxidase activities, with the same Km for arachidonate of 8 micromolar and the same ID50 values for reversible inhibition by flurbiprofen at 5 micromolar, flufenamate at 20 micromolar and aspirin at 20 millimolar; however only the native enzyme was irreversibly inactivated by aspirin, so the active site Ser-530 is not essential for catalysis or substrate binding. 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: Remove the serine and the enzyme still works; it is there to be acetylated, not to do the chemistry. organism: Sheep and mouse enzyme tissue_or_cell_type: Recombinant enzyme in Cos-1 cells experimental_model: Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells limitations: The decisive experiment for the mechanism: it separates what the serine does for catalysis from what acetylating it does. Recombinant sheep enzyme, not human enzyme in a tissue. exposure: Serine 530 replaced with alanine, compared with the native enzyme against aspirin and reversible inhibitors evidence_span: {"source_cache": "artifacts/aspirin-research/2108169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50", "start_char": 0, "end_char": 2076, "text_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50"} [asa-p2108169] The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2108169/ DOI: 10.1016/s0021-9258(19)34105-5
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Valeryl (pentanoyl) salicylate was the only compound of eight acyl salicylates to show isozyme selectivity and inhibited human cyclooxygenase-1 much more effectively than cyclooxygenase-2 in a time-dependent manner, inhibited ovine cyclooxygenase-1 but did not inhibit the S530A mutant of ovine cyclooxygenase-1 which is also refractory to acetylsalicylate, so valeryl salicylate acylates the active site serine.

    Valeryl (pentanoyl) salicylate → Cyclooxygenase-1 (PTGS1) source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/7872783.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f7e8a07a2704cb600938505ec51355671355769c01868ed0966731382901425b", "start_char": 0, "end_char": 1756, "text_sha256": "f7e8a07a2704cb600938505ec51355671355769c01868ed0966731382901425b"}
    experimental_model
    Eight acyl salicylates tested against human cyclooxygenase-1 and -2 expressed transiently in cos-1 cells, with the S530A mutant as a control
    exposure
    Valeryl salicylate and related esters compared with acetylsalicylate
    limitations
    Uses the acetylation chemistry as a design principle and confirms the serine requirement with a mutant. Recombinant enzyme and a murine fibroblast line, not human tissue.
    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
    Human and sheep enzyme
    plain_language
    Swap aspirin’s acetyl group for a bigger one and you get a drug that hits only the first enzyme.
    primary_references
    [asa-p7872783] Selective inhibition of prostaglandin endoperoxide synthase-1 (cyclooxygenase-1) by valerylsalicylic acid. (1995). https://pubmed.ncbi.nlm.nih.gov/7872783/ DOI: 10.1006/abbi.1995.1130
    tissue_or_cell_type
    Recombinant cyclooxygenase

    Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 182–193

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight acyl salicylates tested against human cyclooxygenase-1 and -2 expressed transiently in cos-1 cells, with the S530A mutant as a control · source_derived_draft · unverified_draft

    ### asa-bigger-acyl-group-selective Valeryl (pentanoyl) salicylate was the only compound of eight acyl salicylates to show isozyme selectivity and inhibited human cyclooxygenase-1 much more effectively than cyclooxygenase-2 in a time-dependent manner, inhibited ovine cyclooxygenase-1 but did not inhibit the S530A mutant of ovine cyclooxygenase-1 which is also refractory to acetylsalicylate, so valeryl salicylate acylates the active site serine. 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: Swap aspirin’s acetyl group for a bigger one and you get a drug that hits only the first enzyme. organism: Human and sheep enzyme tissue_or_cell_type: Recombinant cyclooxygenase experimental_model: Eight acyl salicylates tested against human cyclooxygenase-1 and -2 expressed transiently in cos-1 cells, with the S530A mutant as a control limitations: Uses the acetylation chemistry as a design principle and confirms the serine requirement with a mutant. Recombinant enzyme and a murine fibroblast line, not human tissue. exposure: Valeryl salicylate and related esters compared with acetylsalicylate evidence_span: {"source_cache": "artifacts/aspirin-research/7872783.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f7e8a07a2704cb600938505ec51355671355769c01868ed0966731382901425b", "start_char": 0, "end_char": 1756, "text_sha256": "f7e8a07a2704cb600938505ec51355671355769c01868ed0966731382901425b"} [asa-p7872783] Selective inhibition of prostaglandin endoperoxide synthase-1 (cyclooxygenase-1) by valerylsalicylic acid. (1995). https://pubmed.ncbi.nlm.nih.gov/7872783/ DOI: 10.1006/abbi.1995.1130
    Complete structured claim and evidence

  2. The Ala530 mutant of prostaglandin endoperoxide synthase had both cyclooxygenase and hydroperoxidase activity while the Asn530 mutant lacked cyclooxygenase activity but retained hydroperoxidase activity, establishing that the hydroxyl group of Ser530 is not essential for catalysis or substrate binding and suggesting that a bulky group at position 530, such as that introduced by aspirin acetylation, prevents arachidonate binding to the cyclooxygenase active site.

    Cyclooxygenase-1 with asparagine substituted at position 530 → The cyclooxygenase activity of prostaglandin endoperoxide synthase source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/2144687.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24", "start_char": 0, "end_char": 1595, "text_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24"}
    experimental_model
    Sequence comparison and site-directed mutagenesis across sheep, mouse and human prostaglandin endoperoxide synthase
    exposure
    Ser530 replaced with alanine and with asparagine, and tetranitromethane modification with ibuprofen protection
    limitations
    Extends the single mutant to a pair that differ in bulk. Sequence-based assignment of the heme ligands is inference from similarity, not structure.
    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
    Sheep, mouse and human enzyme
    plain_language
    Swap in a small residue and the enzyme is fine; swap in a bigger one and the cyclooxygenase half stops.
    primary_references
    [asa-p2144687] Structure-function relationships in sheep, mouse, and human prostaglandin endoperoxide G/H synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2144687/
    tissue_or_cell_type
    Recombinant enzyme

    Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 104–115

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequence comparison and site-directed mutagenesis across sheep, mouse and human prostaglandin endoperoxide synthase · source_derived_draft · unverified_draft

    ### asa-bulk-not-identity The Ala530 mutant of prostaglandin endoperoxide synthase had both cyclooxygenase and hydroperoxidase activity while the Asn530 mutant lacked cyclooxygenase activity but retained hydroperoxidase activity, establishing that the hydroxyl group of Ser530 is not essential for catalysis or substrate binding and suggesting that a bulky group at position 530, such as that introduced by aspirin acetylation, prevents arachidonate binding to the cyclooxygenase active site. 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: Swap in a small residue and the enzyme is fine; swap in a bigger one and the cyclooxygenase half stops. organism: Sheep, mouse and human enzyme tissue_or_cell_type: Recombinant enzyme experimental_model: Sequence comparison and site-directed mutagenesis across sheep, mouse and human prostaglandin endoperoxide synthase limitations: Extends the single mutant to a pair that differ in bulk. Sequence-based assignment of the heme ligands is inference from similarity, not structure. exposure: Ser530 replaced with alanine and with asparagine, and tetranitromethane modification with ibuprofen protection evidence_span: {"source_cache": "artifacts/aspirin-research/2144687.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24", "start_char": 0, "end_char": 1595, "text_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24"} [asa-p2144687] Structure-function relationships in sheep, mouse, and human prostaglandin endoperoxide G/H synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2144687/
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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