{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:20:31Z","timestamp":1791141631079,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,1,5]]},"abstract":"<jats:p>\n                    Pain associated with inflammation involves prostaglandins synthesized from arachidonic acid (AA) through cyclooxygenase-2 (COX-2) pathways while thromboxane A\n                    <jats:sub>2<\/jats:sub>\n                    formed by platelets from AA via cyclooxygenase-1 (COX-1) mediates thrombosis. COX-1 and COX-2 are both targets of nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) including aspirin whereas COX-2 activity is preferentially blocked by COX-2 inhibitors called coxibs. COXs are homodimers composed of identical subunits, but we have shown that only one subunit is active at a time during catalysis; moreover, many nsNSAIDS bind to a single subunit of a COX dimer to inhibit the COX activity of the entire dimer. Here, we report the surprising observation that celecoxib and other coxibs bind tightly to a subunit of COX-1. Although celecoxib binding to one monomer of COX-1 does not affect the normal catalytic processing of AA by the second, partner subunit, celecoxib does interfere with the inhibition of COX-1 by aspirin in\u00a0vitro. X-ray crystallographic results obtained with a celecoxib\/COX-1 complex show how celecoxib can bind to one of the two available COX sites of the COX-1 dimer. Finally, we find that administration of celecoxib to dogs interferes with the ability of a low dose of aspirin to inhibit AA-induced ex\u00a0vivo platelet aggregation. COX-2 inhibitors such as celecoxib are widely used for pain relief. Because coxibs exhibit cardiovascular side effects, they are often prescribed in combination with low-dose aspirin to prevent thrombosis. Our studies predict that the cardioprotective effect of low-dose aspirin on COX-1 may be blunted when taken with coxibs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0909765106","type":"journal-article","created":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T21:54:06Z","timestamp":1259704446000},"page":"28-33","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":189,"title":["Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1"],"prefix":"10.1073","volume":"107","author":[{"given":"Gilad","family":"Rimon","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Clinical Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjinder S.","family":"Sidhu","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Adam","family":"Lauver","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jullia Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan P.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan A.","family":"Frieler","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Trievel","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict R.","family":"Lucchesi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,11,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"15451","DOI":"10.1021\/bi026938h","article-title":"The cyclooxygenase reaction mechanism","volume":"41","author":"van der Donk W","year":"2002","unstructured":"W van der Donk, A Tsai, R Kulmacz, The cyclooxygenase reaction mechanism. Biochemistry 41, 15451\u201315458 (2002).","journal-title":"Biochemistry"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1021\/cr000068x","article-title":"Mechanism of free radical oxygenation of polyunsaturated fatty acids by cyclooxygenases","volume":"103","author":"Rouzer C","year":"2003","unstructured":"C Rouzer, L Marnett, Mechanism of free radical oxygenation of polyunsaturated fatty acids by cyclooxygenases. Chem Rev 103, 2239\u20132304 (2003).","journal-title":"Chem Rev"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tibs.2007.09.013","article-title":"Nutritionally essential fatty acids and biologically indispensable cyclooxygenases","volume":"33","author":"Smith WL","year":"2008","unstructured":"WL Smith, Nutritionally essential fatty acids and biologically indispensable cyclooxygenases. Trends Biochem Sci 33, 27\u201337 (2008).","journal-title":"Trends Biochem Sci"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.chembiol.2007.04.007","article-title":"Control of oxygenation in lipoxygenase and cyclooxygenase catalysis","volume":"14","author":"Schneider C","year":"2007","unstructured":"C Schneider, DA Pratt, NA Porter, AR Brash, Control of oxygenation in lipoxygenase and cyclooxygenase catalysis. Chem Biol 14, 473\u2013488 (2007).","journal-title":"Chem Biol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"8065","DOI":"10.1074\/jbc.R800005200","article-title":"Non-redundant Functions of Cyclooxygenases: Oxygenation of Endocannabinoids","volume":"283","author":"Rouzer CA","year":"2008","unstructured":"CA Rouzer, LJ Marnett, Non-redundant Functions of Cyclooxygenases: Oxygenation of Endocannabinoids. J Biol Chem 283, 8065\u20138069 (2008).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/JCI27291","article-title":"Biological basis for the cardiovascular consequences of COX-2 inhibition: Therapeutic challenges and opportunities","volume":"116","author":"Grosser T","year":"2006","unstructured":"T Grosser, S Fries, GA FitzGerald, Biological basis for the cardiovascular consequences of COX-2 inhibition: Therapeutic challenges and opportunities. J Clin Invest 116, 4\u201315 (2006).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"6142","DOI":"10.1073\/pnas.0601805103","article-title":"Partnering between monomers of cyclooxygenase-2 homodimers","volume":"103","author":"Yuan C","year":"2006","unstructured":"C Yuan, CJ Rieke, G Rimon, BA Wingerd, WL Smith, Partnering between monomers of cyclooxygenase-2 homodimers. Proc Natl Acad Sci USA 103, 6142\u20136147 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"10046","DOI":"10.1074\/jbc.M808634200","article-title":"Cyclooxygenase allosterism, fatty acid-mediated cross-talk between monomers of cyclooxygenase homodimers","volume":"284","author":"Yuan C","year":"2009","unstructured":"C Yuan, et al., Cyclooxygenase allosterism, fatty acid-mediated cross-talk between monomers of cyclooxygenase homodimers. J Biol Chem 284, 10046\u201310055 (2009).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"12572","DOI":"10.1016\/S0021-9258(17)38909-3","article-title":"Stoichiometry and kinetics of the interaction of prostaglandin H synthase with anti-inflammatory agents","volume":"260","author":"Kulmacz RJ","year":"1985","unstructured":"RJ Kulmacz, WEM Lands, Stoichiometry and kinetics of the interaction of prostaglandin H synthase with anti-inflammatory agents. J Biol Chem 260, 12572\u201312578 (1985).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"7353","DOI":"10.1021\/bi900999z","article-title":"Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid","volume":"49","author":"Prusakiewicz J","year":"2009","unstructured":"J Prusakiewicz, K Duggan, C Rouzer, L Marnett, Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid. Biochemistry 49, 7353\u20137355 (2009).","journal-title":"Biochemistry"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1388-1981(99)00105-5","article-title":"PGHS-2 inhibitors, NS-398 and DuP-697, attenuate the inhibition of PGHS-1 by aspirin and indomethacin without altering its activity","volume":"1440","author":"Rosenstock M","year":"1999","unstructured":"M Rosenstock, A Danon, G Rimon, PGHS-2 inhibitors, NS-398 and DuP-697, attenuate the inhibition of PGHS-1 by aspirin and indomethacin without altering its activity. Biochim Biophys Acta 1440, 127\u2013137 (1999).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0014-2999(00)00931-6","article-title":"Prostaglandin H synthase-2 inhibitors interfere with prostaglandin H synthase-1 inhibition by nonsteroidal anti-inflammatory drugs","volume":"412","author":"Rosenstock M","year":"2001","unstructured":"M Rosenstock, A Danon, M Rubin, G Rimon, Prostaglandin H synthase-2 inhibitors interfere with prostaglandin H synthase-1 inhibition by nonsteroidal anti-inflammatory drugs. Eur J Pharmacol 412, 101\u2013108 (2001).","journal-title":"Eur J Pharmacol"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0014-2999(02)02450-0","article-title":"On the interaction of specific prostaglandin H synthase-2 inhibitors with prostaglandin H synthase-1","volume":"453","author":"Burde T","year":"2002","unstructured":"T Burde, G Rimon, On the interaction of specific prostaglandin H synthase-2 inhibitors with prostaglandin H synthase-1. Eur J Pharmacol 453, 167\u2013173 (2002).","journal-title":"Eur J Pharmacol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"14583","DOI":"10.1073\/pnas.251543298","article-title":"A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin","volume":"98","author":"Ouellet M","year":"2001","unstructured":"M Ouellet, D Riendeau, MD Percival, A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin. Proc Natl Acad Sci USA 98, 14583\u201314588 (2001).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1177\/009127002401102858","article-title":"Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers","volume":"42","author":"K Wilner","year":"2002","unstructured":"Wilner K, et al., Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers. J Clin Pharmacol 42, 1027\u20131030 (2002).","journal-title":"J Clin Pharmacol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.amjcard.2007.11.054","article-title":"The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers","volume":"101","author":"Gladding P","year":"2008","unstructured":"P Gladding, et al., The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers. Am J Cardiol 101, 1060\u20131063 (2008).","journal-title":"Am J Cardiol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1177\/009127000004001224","article-title":"A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers","volume":"40","author":"Greenberg HE","year":"2000","unstructured":"HE Greenberg, et al., A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers. J Clin Pharmacol 40, 1509\u20131515 (2000).","journal-title":"J Clin Pharmacol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa003199","article-title":"Cyclooxygenase inhibitors and the antiplatelet effects of aspirin","volume":"345","author":"Catella-Lawson F","year":"2001","unstructured":"F Catella-Lawson, et al., Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 345, 1809\u20131817 (2001).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1161\/CIRCULATIONAHA.108.764530","article-title":"Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: The cross trial safety analysis","volume":"117","author":"Solomon SD","year":"2008","unstructured":"SD Solomon, et al., Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: The cross trial safety analysis. Circulation 117, 2104\u20132113 (2008).","journal-title":"Circulation"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1161\/hc3301.092790","article-title":"Effects of selective cyclooxygenase-2 inhibition on vascular responses and thrombosis in canine coronary arteries","volume":"104","author":"Hennan JK","year":"2001","unstructured":"JK Hennan, et al., Effects of selective cyclooxygenase-2 inhibition on vascular responses and thrombosis in canine coronary arteries. Circulation 104, 820\u2013825 (2001).","journal-title":"Circulation"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"11202","DOI":"10.1073\/pnas.91.23.11202","article-title":"Mechanism of selective inhibition of the inducible isoform of prostaglandin G\/H synthase","volume":"91","author":"Copeland RA","year":"1994","unstructured":"RA Copeland, et al., Mechanism of selective inhibition of the inducible isoform of prostaglandin G\/H synthase. Proc Natl Acad Sci USA 91, 11202\u201311206 (1994).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0022-3565(25)23861-7","article-title":"Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs","volume":"271","author":"Laneuville O","year":"1994","unstructured":"O Laneuville, et al., Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther 271, 927\u2013934 (1994).","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"17109","DOI":"10.1074\/jbc.274.24.17109","article-title":"The role of arginine 120 of human prostaglandin endoperoxide H synthase-2 in the interaction with fatty acid substrates and inhibitors","volume":"274","author":"Rieke CJ","year":"1999","unstructured":"CJ Rieke, AM Mulichak, RM Garavito, WL Smith, The role of arginine 120 of human prostaglandin endoperoxide H synthase-2 in the interaction with fatty acid substrates and inhibitors. J Biol Chem 274, 17109\u201317114 (1999).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1042\/bj3570709","article-title":"A three-step kinetic mechanism for selective inhibition of cyclo-oxygenase-2 by diarylheterocyclic inhibitors","volume":"357","author":"Walker M","year":"2001","unstructured":"M Walker, et al., A three-step kinetic mechanism for selective inhibition of cyclo-oxygenase-2 by diarylheterocyclic inhibitors. Biochem J 357, 709\u2013718 (2001).","journal-title":"Biochem J"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1096\/fj.05-5273com","article-title":"Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases","volume":"20","author":"Liu W","year":"2006","unstructured":"W Liu, D Cao, SF Oh, CN Serhan, RJ Kulmacz, Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases. FASEB J 20, 1097\u20131108 (2006).","journal-title":"FASEB J"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.clpt.2006.08.021","article-title":"The cyclooxygenase 2 genetic variant -765G>C does not modulate the effects of celecoxib on prostaglandin E2 production","volume":"80","author":"Skarke C","year":"2006","unstructured":"C Skarke, et al., The cyclooxygenase 2 genetic variant -765G>C does not modulate the effects of celecoxib on prostaglandin E2 production. Clin Pharmacol Ther 80, 621\u2013632 (2006).","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/bmc.973","article-title":"Determination of acetylsalicylic acid and its major metabolite, salicylic acid, in human plasma using liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study of Astrix in Korean healthy volunteers","volume":"22","author":"Bae SK","year":"2008","unstructured":"SK Bae, et al., Determination of acetylsalicylic acid and its major metabolite, salicylic acid, in human plasma using liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study of Astrix in Korean healthy volunteers. Biomed Chromatogr 22, 590\u2013595 (2008).","journal-title":"Biomed Chromatogr"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1177\/0091270007313324","article-title":"Prevalence of platelet nonresponsiveness to aspirin in patients treated for secondary stroke prophylaxis and in patients with recurrent ischemic events","volume":"48","author":"Gengo FM","year":"2008","unstructured":"FM Gengo, et al., Prevalence of platelet nonresponsiveness to aspirin in patients treated for secondary stroke prophylaxis and in patients with recurrent ischemic events. J Clin Pharmacol 48, 335\u2013343 (2008).","journal-title":"J Clin Pharmacol"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0026-895X(24)23023-6","article-title":"Cox-2-selective inhibitors: The new super aspirins","volume":"55","author":"DeWitt DL","year":"1999","unstructured":"DL DeWitt, Cox-2-selective inhibitors: The new super aspirins. Mol Pharmacol 55, 625\u2013631 (1999).","journal-title":"Mol Pharmacol"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"278","DOI":"10.2174\/092986708783497247","article-title":"Nimesulide is a selective COX-2 inhibitory, atypical non-steroidal anti-inflammatory drug","volume":"15","author":"Suleyman H","year":"2008","unstructured":"H Suleyman, E Cadirci, Nimesulide is a selective COX-2 inhibitory, atypical non-steroidal anti-inflammatory drug. Curr Med Chem 15, 278\u2013283 (2008).","journal-title":"Curr Med Chem"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/nsb1196-927","article-title":"Flexibility of the NSAID binding site in the structure of human cylcooxygenase-2","volume":"3","author":"Luong C","year":"1996","unstructured":"C Luong, et al., Flexibility of the NSAID binding site in the structure of human cylcooxygenase-2. Nat Struct Biol 3, 927\u2013933 (1996).","journal-title":"Nat Struct Biol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/384644a0","article-title":"Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents","volume":"384","author":"Kurumbail RG","year":"1996","unstructured":"RG Kurumbail, et al., Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature 384, 644\u2013648 (1996).","journal-title":"Nature"},{"key":"e_1_3_4_33_2","first-page":"1933","article-title":"The x-ray crystal structure of prostaglandin endoperoxide H synthase-1 complexed with arachidonic acid","volume":"289","author":"Malkowski MG","year":"2000","unstructured":"MG Malkowski, S Ginell, WL Smith, RM Garavito, The x-ray crystal structure of prostaglandin endoperoxide H synthase-1 complexed with arachidonic acid. Science 289, 1933\u20131937 (2000).","journal-title":"Science"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"18233","DOI":"10.1074\/jbc.M701235200","article-title":"Prostaglandin endoperoxide H synthases: Peroxidase hydroperoxide specificity and cyclooxygenase activation","volume":"282","author":"Liu J","year":"2007","unstructured":"J Liu, et al., Prostaglandin endoperoxide H synthases: Peroxidase hydroperoxide specificity and cyclooxygenase activation. J Biol Chem 282, 18233\u201318244 (2007).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"22254","DOI":"10.1074\/jbc.M703169200","article-title":"Specificities of enzymes and receptors of prostaglandin pathways with arachidonic acid and eicosapentaenoic acid derived substrates and products","volume":"282","author":"Wada M","year":"2007","unstructured":"M Wada, et al., Specificities of enzymes and receptors of prostaglandin pathways with arachidonic acid and eicosapentaenoic acid derived substrates and products. J Biol Chem 282, 22254\u201322266 (2007).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/j.bcp.2007.12.005","article-title":"Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase","volume":"75","author":"Bala M","year":"2008","unstructured":"M Bala, et al., Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase. Biochem Pharmacol 75, 1472\u20131481 (2008).","journal-title":"Biochem Pharmacol"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"42929","DOI":"10.1074\/jbc.M403013200","article-title":"Crystal structure of arachidonic acid bound to a mutant of prostaglandin endoperoxide H synthase-1 that forms predominantly 11-hydroperoxyeicosatetraenoic acid","volume":"279","author":"Harman CA","year":"2004","unstructured":"CA Harman, CJ Rieke, RM Garavito, WL Smith, Crystal structure of arachidonic acid bound to a mutant of prostaglandin endoperoxide H synthase-1 that forms predominantly 11-hydroperoxyeicosatetraenoic acid. J Biol Chem 279, 42929\u201342935 (2004).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"28096","DOI":"10.1074\/jbc.M701335200","article-title":"Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-{alpha}-substituted indomethacin ethanolamides","volume":"282","author":"Harman CA","year":"2007","unstructured":"CA Harman, et al., Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-{alpha}-substituted indomethacin ethanolamides. J Biol Chem 282, 28096\u201328105 (2007).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of x-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski Z","year":"1997","unstructured":"Z Otwinowski, W Minor, Processing of x-ray diffraction data collected in oscillation mode. Method Enzymol 276, 307\u2013326 (1997).","journal-title":"Method Enzymol"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1107\/S0907444905001617","article-title":"Likelihood-enhanced fast translation functions","volume":"61","author":"McCoy AJ","year":"2005","unstructured":"AJ McCoy, RW Grosse-Kunstleve, LC Storoni, RJ Read, Likelihood-enhanced fast translation functions. Acta Crystallogr D 61, 458\u2013464 (2005).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1107\/S0907444902016657","article-title":"PHENIX: Building new software for automated crystallographic structure determination","volume":"58","author":"Adams PD","year":"2002","unstructured":"PD Adams, et al., PHENIX: Building new software for automated crystallographic structure determination. Acta Crystallogr D 58, 1948\u20131954 (2002).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"PRODRG: A tool for high-throughput crystallography of protein-ligand complexes","volume":"60","author":"Schuttelkopf AW","year":"2004","unstructured":"AW Schuttelkopf, DM van Aalten, PRODRG: A tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D 60, 1355\u20131363 (2004).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: Model-building tools for molecular graphics","volume":"60","author":"Emsley P","year":"2004","unstructured":"P Emsley, K Cowtan, Coot: Model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski RA","year":"1993","unstructured":"RA Laskowski, MW MacArthur, DS Moss, JM Thornton, PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Cryst 26, 283\u2013291 (1993).","journal-title":"J Appl Cryst"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"W375","DOI":"10.1093\/nar\/gkm216","article-title":"MolProbity: all-atom contacts and structure validation for proteins and nucleic acids","volume":"35","author":"Davis IW","year":"2007","unstructured":"IW Davis, et al., MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res 35, W375\u2013383 (2007).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/bioinformatics\/15.4.327","article-title":"Automated analysis of interatomic contacts in proteins","volume":"15","author":"Sobolev V","year":"1999","unstructured":"V Sobolev, A Sorokine, J Prilusky, E Abola, M Edelman, Automated analysis of interatomic contacts in proteins. Bioinformatics 15, 327\u2013332 (1999).","journal-title":"Bioinformatics"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S0968-0004(97)01140-7","article-title":"PDBsum: A web-based database of summaries and analyses of all PDB structures","volume":"22","author":"Laskowski R","year":"1997","unstructured":"R Laskowski, et al., PDBsum: A web-based database of summaries and analyses of all PDB structures. Trends Biochem Sci 22, 488\u2013490 (1997).","journal-title":"Trends Biochem Sci"},{"key":"e_1_3_4_48_2","volume-title":"The PyMOL Molecular Graphics System","author":"DeLano WL","year":"2008","unstructured":"WL DeLano The PyMOL Molecular Graphics System (DeLano Scientific, Palo Alto, CA, 2008)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0909765106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T10:22:31Z","timestamp":1739442151000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0909765106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,30]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,1,5]]}},"alternative-id":["10.1073\/pnas.0909765106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0909765106","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1355985.1829054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1355985.827088","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,30]]},"assertion":[{"value":"2009-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-11-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}