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Chemistry and Biochemistry
University of California
230 Physical Sciences Bldg.
Santa Cruz, CA 95064
Phone: (831) 459-4002
Fax: (831) 459-2935
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Theodore Holman Professor of Bioinorganic Chemistry and Biochemistry B.A., University of California, San Diego Ph.D., University of Minnesota, Minneapolis Office: 250 PSB Phone: (831) 459-5884 Fax: (831) 459-2935 tholman@chemistry.ucsc.edu

Holman Research Group Department of Chemistry University of California 1156 High Street Santa Cruz, CA 95064 Office Hours Class Times & Locations Labs: 295/287 PSB, 9-3871 Holman Research Group

RESEARCH INTERESTS: Bioinorganic Chemistry, Lipoxygenase, Heme Binding

Bioinorganic chemistry is a fascinating and challenging discipline at the interface of biochemistry and chemistry. Many critical processes require metal ions, such as respiration, photosynthesis and signal transduction, to name a few. Our research group utilizes enzymology, site directed mutagenesis, molecular biology, inorganic chemistry, and spectroscopy to investigate the biological function of metalloproteins from a rigorous chemical perspective. Specifically, we study the biological function of lipoxygenase in order to understand its mechanism better and discover novel inhibitors.

Human and Soybean Lipoxygenase: Structure/Function Relationships

Soybean lipoxygenase (SLO) is directly involved in soybean germination and senesance, while HLO has been implicated in a variety of diseases (asthma, atherosclerosis, and cancer) and is currently an important pharmaceutical target. Lipoxygenases are non-heme iron enzymes which react with linoleic acid to yield a hydroperoxide product.

The iron atom in lipoxygenases is essential for enzymatic activity and we believe that the reduction potential of the iron atom is critical for the reaction. In our lab, we modify the iron environment (i.e. its redox potential) through site directed mutagenesis and correlate any spectroscopic changes with changes in their kinetic properties. In this manner, we are answering the important question of how the structure of the iron environment relates to its enzymatic function. This knowledge, in turn, may help in the discovery of new potent inhibitors of human lipoxygenase.

Lipoxygenase Inhibitor Discovery

Our lab is also interested in the discovery and characterization of novel inhibitors to lipoxygenase. We currently have discovered over 20 unique lipoxygenase inhibitors through screening the marine natural products (MNP) library of our collaborator, Prof. Phil Crews. The library of Prof. Crews' is one of the worlds largest and offers a unique source of novel chemical structures unavailable through standard synthetic or combinatorial methods. We shall screen this library with a newly developed high thru-put lipoxygenase assay which should increase our inhibitor discovery dramatically. These inhibitors will then be investigated with biochemical and spectroscopic methods to determine how they bind and inhibit lipoxygenase.

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