Fatty Acid Binding to the Allosteric Subunit of Cyclooxygenase-2 Relieves a Tonic Inhibition of the Catalytic Subunit.

ABSTRACT: Prostaglandin endoperoxide H synthase-2 (PGHS-2), also called cyclooxygenase-2 (COX-2), converts arachidonic acid to PGH₂ PGHS-2 is a conformational heterodimer composed of allosteric (E_allo) and catalytic (E_cat) subunits. Fatty acids (FAs) bind to Arg-120 of E_allo increasing to different degrees, depending on the FA, the V_max of its E_cat partner. We report here that movement of helical residues 120-122 and loop residues 123-129 of E_allo underlies the allosteric effects of FAs and allosteric COX-2 inhibitors, including naproxen and flurbiprofen. An S121P substitution in both PGHS-2 monomers yields a variant (S121P/S121P PGHS-2) that has 1.7-1.8 times the V_max of native PGHS-2 and is relatively insensiti

SUBMITTER: Dong L 

PROVIDER: S-EPMC5207261 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature