Project abstract for group lipscomb

Structure and Mechanism of Oxygenase Enzymes

Oxygenase enzymes utilize O2 to oxidize a wide range of biological and manmade compounds with the incorporation of one or both atoms of oxygen into the products. These researchers are using MSI labs for two projects concerning these enzymes. In the first project, the researchers are studying a series of dioxygenase enzymes, which attack aromatic compounds. The products are ring open compounds containing both atoms of oxygen from O2. These 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 allows manmade aromatics, some of which are carcinogens, to be degraded. In collaboration with Professor Douglas Ohlendorf’s group, these researchers have solved the crystal structures of three of these enzymes. MSI is being used to examine the crystal structures and to plan site directed mutagenesis studies. Also, together with Dr. Kovaleva, they have recently been able to structurally characterize the first reaction cycle intermediates by carrying out the reaction in a crystal and analyzing the data at the MSI.

The second class of oxygenase being studied is typified by methane monooxygenase. 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 Professor Ohlendorf, the group has solved the crystal structure of the critical hydroxylase component and is using the BSCL to visualize the structure and plan mutagenesis studies. Recently, the researchers have discovered a new member of this family that is responsible for the biosynthesis of many antibiotics. The structural data for this new enzyme is being analyzed using MSI. The first structure has now been solved opening the door to the family.

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