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Acetylation of Ser530 inhibits catalysis by preventing access of arachidonic acid substrate in the COX\u20101 isoenzyme. Acetylated COX\u20102, in contrast, gains a new catalytic activity and forms\n                    <jats:italic>15R<\/jats:italic>\n                    hydroxy\u2010eicosatetraenoic acid (15R\u2010HETE) as alternate product. Here we show that acetylated COX\u20102 also retains COX activity, forming predominantly 15R\u2010configuration PGs (70 or 62% 15\n                    <jats:italic>R<\/jats:italic>\n                    , respectively, determined using radiolabeled substrate or LC\u2010MS analysis). Although the\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>m<\/jats:sub>\n                    of arachidonic acid for acetylated COX\u20102 was ~3\u2010fold lower than for uninhibited COX\u20102, the catalytic efficiency for PG formation by the acetylated enzyme was reduced 10\u2010fold due to a concomitant decrease in\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    . Aspirin increased 15\n                    <jats:italic>R<\/jats:italic>\n                    \u2010PGD\n                    <jats:sub>2<\/jats:sub>\n                    but not 15\n                    <jats:italic>R<\/jats:italic>\n                    \u2010PGE\n                    <jats:sub>2<\/jats:sub>\n                    in isolated human leukocytes activated with LPS to induce COX\u20102.15\n                    <jats:italic>R<\/jats:italic>\n                    \u2010PGD\n                    <jats:sub>2<\/jats:sub>\n                    inhibited human platelet aggregation induced by the thromboxane receptor agonist U46,619, and this effect was abrogated by an antagonist of the DPI prostanoid receptor. We conclude that acetylation of Ser530 in COX\u20102 not only triggers formation of 15R\u2010HETE but also allows oxygenation and cyclization of arachidonic acid to a 15\n                    <jats:italic>R<\/jats:italic>\n                    \u2010PG endoperoxide. 15\n                    <jats:italic>R<\/jats:italic>\n                    \u2010PGs are novel products of aspirin therapy\n                    <jats:italic>via<\/jats:italic>\n                    acetylation of COX\u20102 and may contribute to its antiplatelet and other pharmacologic effects.\u2014Gim\u00e9nez\u2010Bastida, J. A., Boeglin, W. E., Boutaud, O., Malkowski, M. G., Schneider, C. Residual cyclooxygenase activity of aspirin\u2010acetylated COX\u20102 forms 15R\u2010prostaglandins that inhibit platelet aggregation. FASEB J. 33, 1033\u20131041 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801018r","type":"journal-article","created":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T14:27:12Z","timestamp":1533911232000},"page":"1033-1041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Residual cyclooxygenase activity of aspirin\u2010acetylated COX\u20102 forms 15\n                    <i>R<\/i>\n                    \u2010prostaglandins that inhibit platelet aggregation"],"prefix":"10.1096","volume":"33","author":[{"given":"Juan A.","family":"Gim\u00e9nez-Bastida","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Department of Pharmacology Vanderbilt University Medical School  Nashville Tennessee USA"},{"name":"Vanderbilt Institute of Chemical Biology Vanderbilt University Medical School  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Boeglin","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Pharmacology Vanderbilt University Medical School  Nashville Tennessee USA"},{"name":"Vanderbilt Institute of Chemical Biology Vanderbilt University Medical School  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Boutaud","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Pharmacology Vanderbilt University Medical School  Nashville Tennessee USA"},{"name":"Vanderbilt Institute of Chemical Biology Vanderbilt University Medical School  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Malkowski","sequence":"additional","affiliation":[{"name":"Department of 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