期刊论文详细信息
FEBS Letters
Mutation of serine‐516 in human prostaglandin G/H synthase‐2 to methionine or aspirin acetylation of this residue stimulates 15‐R‐HETE synthesis
Mancini, Joseph A.1  Vickers, Philip J.1  Bayly, Christopher2  O'Neill, Gary P.1 
[1] Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Kirkland, Que., H9R 4P8, Canada;Department of Biochemistry and Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Kirkland, Que., H9R 4P8, Canada
关键词: Prostaglandin G/H synthase-2;    PGHS-2;    Cyclooxygenase-2;    COX-2;    15-HETE;    Mutagenesis;    Vaccinia virus;    ASA;    acetylsalicylic acid;    DMSO;    dimethyl sulphoxide;    EDTA;    ethylenediamine tetraacetic acid;    11-HETE;    11-hydroxyeicosatetraenoic acid;    15-HETE;    15-hydroxyeicosatetraenoic acid;    NSAIDS;    non-steroidal antiinflammatory drugs;    PG;    prostaglandin;    PGHS;    prostaglandin G/H synthase;    SDS-PAGE;    sodium dodecyl sulphate polyacrylamide gel electrophoresis;   
DOI  :  10.1016/0014-5793(94)80579-2
学科分类:生物化学/生物物理
来源: John Wiley & Sons Ltd.
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【 摘 要 】

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 Ser516 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.

【 授权许可】

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