Virtuelle (Nano) Welten: PDB Molecule of the Month 17: Cyclooxygenase

A Complex Enzyme

This enzyme actually has two different active sites, collectively termed prostaglandin synthase. On one side, it has the cyclooxygenase active site discussed on the previous page. On the opposite side, is has an entirely separate peroxidase site, which is needed to activate the heme groups that participate in the cyclooxygenase reaction. The enzyme complex is a dimer of identical subunits, so altogether, there are two cyclooxygenase active sites and two peroxidase active sites in close proximity. Each subunit has a small carbon-rich knob, pointing downward in this illustration. These knobs anchor the complex to the membrane of the endoplasmic reticulum, shown in light blue at the bottom of the picture. The cyclooxygenase active site is buried deep within the protein, and is reachable by a tunnel that opens out in the middle of the knob. This acts like a funnel, guiding arachidonic acid out of the membrane and into the enzyme for processing. In the structure shown here, PDB entry 4cox, a drug (yellow and green) is blocking the active site in both subunits. The heme groups are also shown above the drug in each subunit.