Determination of the Structural Environment of the Tyrosyl Radical in Prostaglandin H_2 Synthase-1:A High Frequency ENDOR/EPR Study

摘要

Prostaglandin H_2 Synthase(PGHS)is responsible for the conversion of arachidonic acid(AA)to prostaglandin H_2,the first committed step in the biosynthesis of the prostanoids.Two different isoforms of PGHS have been identified.PGHS-1 is constitutively expressed and appears to function as a housekeeping enzyme,while PGHS-2 can be induced by a wide variety of stimulants and is thought to participate in such diverse physiological and pathological processes as reproduction,cardiovascular function,atherosclerosis,tumorigenesis,and inflammation.The two isoforms have approximately 60% sequence identity and very similar three-dimensional structures,as well as similar kinetic profiles,indicating that they probably share the same basic mechanism.PGHS has two distinct active sites,which are functionally connected by the generation of a radical on Y385(PGHS-1 numbering).