John D. Lipscomb, Principal Investigator

Structure and Mechanism of Oxygenase Enzymes

  Oxygenase enzymes utilize molecular oxygen to oxidize a wide range of biological and manmade compounds with the incorporation of one or both atoms of oxygen from molecular oxygen in the products.

  In the first project undertaken by this group, a series of dioxygenase enzymes was studied. These enzymes attack aromatic substrates with two hydroxyl substituents. The products are ring-open compounds containing both atoms of oxygen from O₂. Their products are easily degraded by bacteria, thus allowing the enormous amounts of carbon stored in aromatic compounds in the environment to reenter the carbon cycle. Also, the dioxygenases allow manmade aromatics, some of which are carcinogens, to be degraded. In collaboration with Dr. Ohlendorf's group, the researchers solved the crystal structures of three of these enzymes. The supercomputing facility was used to examine the crystal structures and plan ongoing, site-directed mutagenesis studies.

  The second class of oxygenase studied was typified by methane monoxygenase. This enzyme catalyzes the oxidation of methane to methanol with the incorporation of one atom of oxygen. Methane is generated in large quantities in the environment and is a potent greenhouse gas. It is prevented from reaching the atmosphere by the action of methane monooxygenase.

  Again, in collaboration with Dr. Ohlendorf, the group solved the crystal structure of the critical hydroxylase component. The supercomputing facility was used to visualize the structure and plan mutagenesis studies.