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Heme prosthetic group required for acetylation of prostaglandin H synthase by aspirin
Author(s) -
Chen YingNan Pan,
Marnett Lawrence J.
Publication year - 1989
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.3.11.2506093
Subject(s) - atp synthase , heme , prostaglandin , aspirin , chemistry , enzyme , acetylation , biochemistry , protein subunit , gene
The ability of aspirin to acetylate PGH synthase was determined by reacting [ 3 H‐acetyl]‐aspirin with purified enzyme followed by high pressure liquid chromatography analysis of the protein components of the reaction mixture. Heme‐reconstituted enzyme incorporated approximately one acetyl group per 70‐kDa subunit, whereas apoprotein incorporated 0.1 acetyl group per subunit. The ability of the heme prosthetic group to enhance acetylation of the protein was correlated with its ability to protect the Arg 253 ‐Gly 254 peptide bond from cleavage by trypsin. Thus, heme‐induced alteration of protein conformation may contribute to the enhanced labeling of Ser 506 by aspirin. The present results indicate that irreversible inactivation of prostaglandin H synthase by aspirin occurs only when the heme prosthetic group is bound to the protein. Considering its short in vivo half‐life, it is likely that aspirin inactivates only the steady‐state fraction of PGH synthase in a cell that is active but not newly synthesized apoprotein. This may contribute to the differential kinetics of inactivation and recovery of PGH synthase activity in platelets and vascular endothelial cells after administration of low dose aspirin as a prophylactic agent against cardiovascular disease.—C hen , Y.‐N. P.; M arnett , L.J. Heme prosthetic group required for acetylation of prostaglandin H synthase by aspirin. FASEB J. 3: 2294‐2297; 1989.