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Michael Toney
Associate Professor

Email: toney@chem.ucdavis.edu
Phone:(530) 754-5282

B.S. in Chemistry, University of Alabama, May 1985.
Ph.D. in Biochemistry, University of California – Berkeley, December 1990.
Cancer Research Coordinating Commitee Fellowship, 1993 – 1994.
National Institutes of Health Postdoctoral Fellowship, 1990 – 1993.
Structural Biology Graduate Research Award, University of California – Berkeley, 1990.
Outstanding Chemistry Undergraduate Award, University of Alabama, 1985.
Group Page
Principal Research Interests
We are interested in both the fundamental and applied aspects of enzyme reaction mechanisms. Enzymes can catalyze reactions by enourmous factors. The sources of the great cataclyic powers of enzymes are generally understood in qualitative terms. These include close approximation of reacting groups in the enzyme substrate complex, general acid base catalysts and so on. A quantitative understanding of these catalytic tools is not available and is one of the goals of our research program. On the applied side, enzymes are often the target of pharmaceuticals. We choose to explore the mechanisms of enzymes that are promising drug targets with the ultimate goal of developing lead compounds for pharmaceutical development.
Representative Publications

Toney, M.D., Hohenester, E., Cowan, S.W., Jansonius, J.N.* (1993) "Dialkylglycine Decarboxylase Structure: Bifunctional Active Site and Alkali Metal Sites", Science 261, 756.

Malashkevich, V., Toney, M.D., Jansonius, J.N.* (1993) "Crystal Structures of True Enzymatic Reaction Intermediates: Aspartate and Glutamate Ketimines of Mitochondrial Aspartate Aminotransferase", Biochemistry 32, 13451.

Toney, M.D., Kirsch, J.F.* (1993) "Lysine-258 in Aspartate Aminotransferase: Enforcer of the Circe Effect for Amino Acid Substrates and General Base Catalyst for the 1,3-Prototropic Shift", Biochemistry 32, 1471.

Toney, M.D., Keller, J.W., Pauptit, R.A., J?ger, J., Wise, M.K., Sauder, U., Jansonius, J.N.* (1991) "Crystallization and Preliminary X?ray Diffraction Studies of Dialkylglycine Decarboxylase, A Decarboxylating Transaminase", J. Mol. Biol. 222, 873.

Toney, M.D., Kirsch, J.F.* (1991) "Br?nsted Analysis of Aspartate Aminotransferase via Exogenous Catalysis of Reactions of an Inactive Mutant", Protein Science 1, 107.

Toney, M.D., Kirsch, J.F.* (1991) "The K258R Mutant of Aspartate Aminotransferase Stabilizes the Quinonoid Intermediate", J. Biol. Chem. 266, 23900.

Toney, M.D., Kirsch, J.F.* (1991) "Tyrosine 70 Fine-Tunes the Catalytic Efficiency of Aspartate Aminotransferase", Biochemistry 30, 7456.

Toney, M.D., Kirsch, J.F.* (1991) "Kinetics and Equilibria for the Reactions of Coenzymes with Wild Type and the Y70F Mutant of Escherichia coli Aspartate Aminotransferase", Biochemistry 30, 7461.

Kirsch, J.F.*, Planas, A., Toney, M.D. (1991) "Genetic Engineering and Chemical Modification at the Position of Lysine 258 in Aspartate Aminotransferase", in Enzymes Dependent on Pyridoxal Phosphate and Other Carbonyl Compounds (T. Fukui, H. Kagamiyama, K. Soda, and H. Wada, eds), Pergamon, Tokyo, p. 161.

Kirsch, J. F.*, Toney, M. D., Goldberg, J. M. (1990) "Chemical Rescue and Change in Rate Determining Steps Elicited by Site-Directed Mutagenesis Probes of Aspartate Aminotransferase", in Protein and Pharmaceutical Engineering. UCLA Symposia on Molecular and Cellular Biology, New Series Volume 110. (C. Craik, R. Fletterick, C.R. Matthews, and J. Wells, eds), p. 105.

Toney, M.D., Kirsch, J.F.* (1989) "Direct Br?nsted Analysis of the Restoration of Activity to a Mutant Enzyme by Exogenous Amines", Science 243, 1485.

Julin, D.A., Wiesinger, H., Toney, M.D., Kirsch, J.F.* (1989) "Estimation of Free Energy Barriers in the Cytoplasmic and Mitochondrial Aspartate Aminotransferase Reactions Probed by Hydrogen Exchange Kinetics of Ca Labeled Amino Acids with Solvent", Biochemistry 28, 3815.

Smith, D.L., Almo, S.C., Toney, M.D., Ringe, D.* (1989) "2.8 ? Resolution Crystal Structure of an Active Site Mutant of Aspartate Aminotransferase from E. coli", Biochemistry 28, 8161.

Hemsley, A., Arnheim, N.*, Toney, M., Cortopassi, G., Galas, D. (1989) "A Simple Method For Site-Directed Mutagenesis Using The Polymerase Chain Reaction", Nucl. Acids Res. 17, 6545.

Kirsch, J. F.*, Toney, M. D. (1989) "Br?nsted Analysis of Enzymatic Proton Transfer Reactions Through Site-Directed Mutagenesis", Ann. New York Acad. Sci. 585, 48.

Toney, M.D., Kirsch, J.F.* (1987) "Tyrosine 70 Increases the Coenzyme Affinity of Aspartate Aminotransferase: A Site-Directed Mutagenesis Study", J. Biol. Chem. 262, 12403.

Kirsch, J.F.*, Finlayson, W.L., Toney, M.D., Cronin, C.N. (1987) "Mechanistic Analysis of the Aspartate Aminotransferase Active Site Mutants - Y70F, K258A, and R292D", in Biochemistry of Vitamin B6: Proceedings of the 7th International Congress on Chemical and Biological Aspects of Vitamin B6 Catalysis (Korpela, T., and Christen, P., eds), Birkhauser, Basel, p. 59.