Interactions of 2-O-arachidonylglycerol ether and ibuprofen with the allosteric and catalytic subunits of human COX-2

• DOI: 10.1194/jlr.m067512
• Publication Date: 2016-04-09T04:04:31Z
• Authors: Liang Dong; Hechang Zou; Chong Yuan; Yu H. Hong; Charis L. Uhlson; Robert C. Murphy; William L. Smith
• Keywords: Ibuprofen

Prostaglandin (PG) endoperoxide H synthase (PGHS)-2, also known as cyclooxygenase (COX)-2, can convert arachidonic acid (AA) to PGH2 in the committed step of PG synthesis. PGHS-2 functions a conformational heterodimer composed an allosteric (Eallo) and catalytic (Ecat) monomer. Here we investigated interplay between human (hu)PGHS-2 alternative COX substrate, endocannabinoid, 2-arachidonoylglycerol (2-AG), well stable analog, 2-O-arachidonylglycerol ether (2-AG ether). We compared inhibition huPGHS-2-mediated oxygenation AA, 2-AG, 2-AG by well-known inhibitor, ibuprofen. When tested with huPGHS-2, exhibit very similar kinetic parameters, responses stimulation FAs that are not substrates, modes The binds Ecat more tightly than Eallo and, thus, be used Ecat-specific substrate examine certain Eallo-dependent responses. Ibuprofen binding huPGHS-2 completely blocks or oxygenation; however, ibuprofen AA engages combination both competitive mechanisms.