Title : Structural insights into the stereochemistry of the cyclooxygenase reaction
Abstract :
- Cyclooxygenases are bifunctional enzymes that catalyse the first committed step in the synthesis of prostaglandins, thromboxanes and other eicosanoids
- The two known cyclooxygenases isoforms share a high degree of amino-acid sequence similarity, structural topology and an identical catalytic mechanism
- Cyclooxygenase enzymes catalyse two sequential reactions in spatially distinct, but mechanistically coupled active sites
- The initial cyclooxygenase reaction converts arachidonic acid (which is achiral) to prostaglandin G2 (which has five chiral centres)
- The subsequent peroxidase reaction reduces prostaglandin G2 to prostaglandin H2
- Here we report the co-crystal structures of murine apo- cyclooxygenase-2 in complex with arachidonic acid and prostaglandin
- These structures suggest the molecular basis for the stereospecificity of prostaglandin G2 synthesis