Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15- R-HETE synthesis
Prostaglandin G/H synthase (PGHS) is a key enzyme in cellular prostaglandin (PG) synthesis and is the target of non-steroidal anti-inflammatory agents. PGHS occurs in two isoforms, termed PGHS-1 and PGHS-2. These isoforms differ in several respects, including their enzymatic activity following acety...
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| Veröffentlicht in: | FEBS letters 1994-03, Vol.342 (1), p.33-37 |
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| description | Prostaglandin G/H synthase (PGHS) is a key enzyme in cellular prostaglandin (PG) synthesis and is the target of non-steroidal anti-inflammatory agents. PGHS occurs in two isoforms, termed PGHS-1 and PGHS-2. These isoforms differ in several respects, including their enzymatic activity following acetylation by aspirin. While PG synthesis by both isoforms is inhibited by aspirin, 15-
R-hydroxyeicosatetraenoic acid (15-
R-HETE) synthesis by PGHS-2, but not PGHS-1, is stimulated by preincubation with aspirin. We have mutated the putative aspirin acetylation site of hPGHS-2, and expressed the mutants in COS-7 cells using recombinant vaccinia virus. Enzyme activity and inhibitor sensitivity studies provide evidence that Ser
516 is the aspirin acetylation site of human PGHS-2 and that substitution of a methionine residue at this position can mimic the effects of aspirin acetylation on enzyme activity. |
| doi_str_mv | 10.1016/0014-5793(94)80579-2 |
| format | Article |
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R-hydroxyeicosatetraenoic acid (15-
R-HETE) synthesis by PGHS-2, but not PGHS-1, is stimulated by preincubation with aspirin. We have mutated the putative aspirin acetylation site of hPGHS-2, and expressed the mutants in COS-7 cells using recombinant vaccinia virus. Enzyme activity and inhibitor sensitivity studies provide evidence that Ser
516 is the aspirin acetylation site of human PGHS-2 and that substitution of a methionine residue at this position can mimic the effects of aspirin acetylation on enzyme activity.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/0014-5793(94)80579-2</identifier><identifier>PMID: 8143845</identifier><identifier>CODEN: FEBLAL</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>11-HETE ; 11-hydroxyeicosatetraenoic acid ; 15-HETE ; 15-hydroxyeicosatetraenoic acid ; Acetylation ; acetylsalicylic acid ; Analytical, structural and metabolic biochemistry ; Animals ; ASA ; Aspirin - metabolism ; Aspirin - pharmacology ; Biological and medical sciences ; Cell Line ; COX-2 ; Cyclooxygenase-2 ; dimethyl sulphoxide ; DMSO ; EDTA ; Enzymes and enzyme inhibitors ; ethylenediamine tetraacetic acid ; Fundamental and applied biological sciences. Psychology ; Humans ; Hydroxyeicosatetraenoic Acids - biosynthesis ; Methionine - chemistry ; Microsomes - metabolism ; Mutagenesis ; Mutagenesis, Site-Directed ; non-steroidal antiinflammatory drugs ; NSAIDS ; Oxidoreductases ; PGHS ; PGHS-2 ; prostaglandin ; prostaglandin G/H synthase ; Prostaglandin G/H synthase-2 ; Prostaglandin-Endoperoxide Synthases - chemistry ; Prostaglandin-Endoperoxide Synthases - genetics ; Prostaglandin-Endoperoxide Synthases - metabolism ; Prostaglandins - biosynthesis ; SDS-PAGE ; Serine - chemistry ; sodium dodecyl sulphate polyacrylamide gel electrophoresis ; Vaccinia virus</subject><ispartof>FEBS letters, 1994-03, Vol.342 (1), p.33-37</ispartof><rights>1994</rights><rights>FEBS Letters 342 (1994) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5262-a7e18d4e5198d73183543436229316b7f205a08df613f703f24fd7f7fbb49a783</citedby><cites>FETCH-LOGICAL-c5262-a7e18d4e5198d73183543436229316b7f205a08df613f703f24fd7f7fbb49a783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0014-5793(94)80579-2$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4069619$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8143845$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mancini, Joseph A.</creatorcontrib><creatorcontrib>O'Neill, Gary P.</creatorcontrib><creatorcontrib>Bayly, Christopher</creatorcontrib><creatorcontrib>Vickers, Philip J.</creatorcontrib><title>Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15- R-HETE synthesis</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>Prostaglandin G/H synthase (PGHS) is a key enzyme in cellular prostaglandin (PG) synthesis and is the target of non-steroidal anti-inflammatory agents. PGHS occurs in two isoforms, termed PGHS-1 and PGHS-2. These isoforms differ in several respects, including their enzymatic activity following acetylation by aspirin. While PG synthesis by both isoforms is inhibited by aspirin, 15-
R-hydroxyeicosatetraenoic acid (15-
R-HETE) synthesis by PGHS-2, but not PGHS-1, is stimulated by preincubation with aspirin. We have mutated the putative aspirin acetylation site of hPGHS-2, and expressed the mutants in COS-7 cells using recombinant vaccinia virus. Enzyme activity and inhibitor sensitivity studies provide evidence that Ser
516 is the aspirin acetylation site of human PGHS-2 and that substitution of a methionine residue at this position can mimic the effects of aspirin acetylation on enzyme activity.</description><subject>11-HETE</subject><subject>11-hydroxyeicosatetraenoic acid</subject><subject>15-HETE</subject><subject>15-hydroxyeicosatetraenoic acid</subject><subject>Acetylation</subject><subject>acetylsalicylic acid</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>ASA</subject><subject>Aspirin - metabolism</subject><subject>Aspirin - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>COX-2</subject><subject>Cyclooxygenase-2</subject><subject>dimethyl sulphoxide</subject><subject>DMSO</subject><subject>EDTA</subject><subject>Enzymes and enzyme inhibitors</subject><subject>ethylenediamine tetraacetic acid</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Hydroxyeicosatetraenoic Acids - biosynthesis</subject><subject>Methionine - chemistry</subject><subject>Microsomes - metabolism</subject><subject>Mutagenesis</subject><subject>Mutagenesis, Site-Directed</subject><subject>non-steroidal antiinflammatory drugs</subject><subject>NSAIDS</subject><subject>Oxidoreductases</subject><subject>PGHS</subject><subject>PGHS-2</subject><subject>prostaglandin</subject><subject>prostaglandin G/H synthase</subject><subject>Prostaglandin G/H synthase-2</subject><subject>Prostaglandin-Endoperoxide Synthases - chemistry</subject><subject>Prostaglandin-Endoperoxide Synthases - genetics</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Prostaglandins - biosynthesis</subject><subject>SDS-PAGE</subject><subject>Serine - chemistry</subject><subject>sodium dodecyl sulphate polyacrylamide gel electrophoresis</subject><subject>Vaccinia virus</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcuKFDEUhoMoYzv6BgpZiOiinNwql82ADt3Twogg4zqkq07sSF3aJKX0Y_jGpqaaXoqrJOf_zp-cPwi9pOQ9JVReEUJFVSvD3xrxTpOyq9gjtKJa8YoLqR-j1Rl5ip6l9IOUs6bmAl1oKrgW9Qr9-Txll8M44NHjBDEMUNVU4jDg_dS7AR_imLL73rmhLbXbqy1OxyHvXYKK4TziHvK-tJc-PEbs0iEUD-wayMfubFyQhCOk0E6AUw79VDRImNYV_lpt1_frxbUQ6Tl64l2X4MVpvUTfNuv7m2119-X2082Hu6qpmWSVU0B1K6CmRreKU81rwQWXjBlO5U55RmpHdOsl5V4R7pnwrfLK73bCOKX5JXqz-JYJf06Qsu1DaqArk8I4JUulIobKGRQL2JQoUgRvDzH0Lh4tJXb-CTvHbOeYrRH24ScsK22vTv7Trof23HSKvuivT7pLjet8dEMT0hkTRBpJTcE2C_Y7dHD8r6vtZv2RzcJcN-KhOr_nejGCEuqvANGmJsDQQBsiNNm2Y_j3QH8Bd423ew</recordid><startdate>19940328</startdate><enddate>19940328</enddate><creator>Mancini, Joseph A.</creator><creator>O'Neill, Gary P.</creator><creator>Bayly, Christopher</creator><creator>Vickers, Philip J.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope></search><sort><creationdate>19940328</creationdate><title>Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15- R-HETE synthesis</title><author>Mancini, Joseph A. ; O'Neill, Gary P. ; Bayly, Christopher ; Vickers, Philip J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5262-a7e18d4e5198d73183543436229316b7f205a08df613f703f24fd7f7fbb49a783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>11-HETE</topic><topic>11-hydroxyeicosatetraenoic acid</topic><topic>15-HETE</topic><topic>15-hydroxyeicosatetraenoic acid</topic><topic>Acetylation</topic><topic>acetylsalicylic acid</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>ASA</topic><topic>Aspirin - metabolism</topic><topic>Aspirin - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>COX-2</topic><topic>Cyclooxygenase-2</topic><topic>dimethyl sulphoxide</topic><topic>DMSO</topic><topic>EDTA</topic><topic>Enzymes and enzyme inhibitors</topic><topic>ethylenediamine tetraacetic acid</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Hydroxyeicosatetraenoic Acids - biosynthesis</topic><topic>Methionine - chemistry</topic><topic>Microsomes - metabolism</topic><topic>Mutagenesis</topic><topic>Mutagenesis, Site-Directed</topic><topic>non-steroidal antiinflammatory drugs</topic><topic>NSAIDS</topic><topic>Oxidoreductases</topic><topic>PGHS</topic><topic>PGHS-2</topic><topic>prostaglandin</topic><topic>prostaglandin G/H synthase</topic><topic>Prostaglandin G/H synthase-2</topic><topic>Prostaglandin-Endoperoxide Synthases - chemistry</topic><topic>Prostaglandin-Endoperoxide Synthases - genetics</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Prostaglandins - biosynthesis</topic><topic>SDS-PAGE</topic><topic>Serine - chemistry</topic><topic>sodium dodecyl sulphate polyacrylamide gel electrophoresis</topic><topic>Vaccinia virus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mancini, Joseph A.</creatorcontrib><creatorcontrib>O'Neill, Gary P.</creatorcontrib><creatorcontrib>Bayly, Christopher</creatorcontrib><creatorcontrib>Vickers, Philip J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mancini, Joseph A.</au><au>O'Neill, Gary P.</au><au>Bayly, Christopher</au><au>Vickers, Philip J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15- R-HETE synthesis</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>1994-03-28</date><risdate>1994</risdate><volume>342</volume><issue>1</issue><spage>33</spage><epage>37</epage><pages>33-37</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><coden>FEBLAL</coden><abstract>Prostaglandin G/H synthase (PGHS) is a key enzyme in cellular prostaglandin (PG) synthesis and is the target of non-steroidal anti-inflammatory agents. PGHS occurs in two isoforms, termed PGHS-1 and PGHS-2. These isoforms differ in several respects, including their enzymatic activity following acetylation by aspirin. While PG synthesis by both isoforms is inhibited by aspirin, 15-
R-hydroxyeicosatetraenoic acid (15-
R-HETE) synthesis by PGHS-2, but not PGHS-1, is stimulated by preincubation with aspirin. We have mutated the putative aspirin acetylation site of hPGHS-2, and expressed the mutants in COS-7 cells using recombinant vaccinia virus. Enzyme activity and inhibitor sensitivity studies provide evidence that Ser
516 is the aspirin acetylation site of human PGHS-2 and that substitution of a methionine residue at this position can mimic the effects of aspirin acetylation on enzyme activity.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>8143845</pmid><doi>10.1016/0014-5793(94)80579-2</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-5793 |
| ispartof | FEBS letters, 1994-03, Vol.342 (1), p.33-37 |
| issn | 0014-5793 1873-3468 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via ScienceDirect (Elsevier); Alma/SFX Local Collection |
| subjects | 11-HETE 11-hydroxyeicosatetraenoic acid 15-HETE 15-hydroxyeicosatetraenoic acid Acetylation acetylsalicylic acid Analytical, structural and metabolic biochemistry Animals ASA Aspirin - metabolism Aspirin - pharmacology Biological and medical sciences Cell Line COX-2 Cyclooxygenase-2 dimethyl sulphoxide DMSO EDTA Enzymes and enzyme inhibitors ethylenediamine tetraacetic acid Fundamental and applied biological sciences. Psychology Humans Hydroxyeicosatetraenoic Acids - biosynthesis Methionine - chemistry Microsomes - metabolism Mutagenesis Mutagenesis, Site-Directed non-steroidal antiinflammatory drugs NSAIDS Oxidoreductases PGHS PGHS-2 prostaglandin prostaglandin G/H synthase Prostaglandin G/H synthase-2 Prostaglandin-Endoperoxide Synthases - chemistry Prostaglandin-Endoperoxide Synthases - genetics Prostaglandin-Endoperoxide Synthases - metabolism Prostaglandins - biosynthesis SDS-PAGE Serine - chemistry sodium dodecyl sulphate polyacrylamide gel electrophoresis Vaccinia virus |
| title | Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15- R-HETE synthesis |
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