Office: Chemistry C215
Phone: (970) 491-6339
- Ph.D. Northwestern University
We are studying the structures of interesting inorganic complexes and selected proteins by means of single crystal X-ray diffraction. In the protein studies, we collaborate closely with colleagues at Colorado State in areas such as biochemistry, microbiology, and physiology. The proteins currently of interest include glutaminase and hexokinase (especially in complex with inorganic polyoxoanions). Diffraction data for inorganic complexes are collected on a Bruker SMART 1000 CCD diffractometer, while data for proteins are collected on a R-Axis-IV X-ray diffractometer. Brief descriptions of our main projects of interest in protein crystallography are as follows. Glutaminase. Our studies on the structure of the enzyme glutaminase are being carried out in collaboration with Professor Norman Curthoys (Department of Biochemistry and Molecular Biology). In the brain, control of glutamate concentration is critical to avoidance of neuronal cell toxicity. Recent studies have implicated glutaminase as an important contributor to the neurotoxic glutamate levels in stroke-damaged brain tissue. We anticipate that determination of the molecular structure of glutaminase will aid in the development of an effective drug therapy that could limit the progressive neuronal atrophy caused by stroke. Hexokinase. Professor Debbie Crans (Department of Chemistry) and her co-workers have shown that a number of inorganic polyoxometalate anions (such as decavanadate, V10O286–) of varying sizes and charges inhibit the first step in the metabolism of glucose, which involves catalysis of phosphorylation by the enzyme hexokinase. Furthermore, the magnitude of the inhibitory effect depends on the charge and size of the polyoxometalate anion. This result demands structural investigation in order to understand its origin and to map out the interactions between proteins and these complex inorganic species, and we are actively collaborating with Professor Crans and her group toward that end. As a result, we are giving heavy emphasis to the determination of the structures of yeast hexokinase B (hkB) in complexation with polyoxometalate anions, so that we can understand the origin(s) of these inhibitory effects. For comparison purposes, we also plan to attempt to co-crystallize hkB in the presence of substrates (sugars, nucleotides and nucleotide analogues).