Chemistry Faculty:
Robert S. Phillips, Ph.D.
Professor
Phone: 706-542-1996
E-mail: phillips@sunchem.chem.uga.edu
Biographical Information
Ph.D., Georgia Institute of Technology, 1979
Research Interests
Enzymes are remarkable biocatalysts, not only for the dramatic rate accelerations (1012-1020 fold) that they provide, but also for the high degree of substrate specificity, regiospecificity and stereospecificity that these reactions exhibit. The work in my laboratory is focused on the chemical basis for how enzymes achieve such high rates and reaction specificity. Two groups of enzymes are currently under study in the laboratory: (1) Pyridoxal 5'-phosphate (PLP; vitamin B6) dependent enzymes; and (2) Alcohol dehydrogenases. Tyrosine phenol-lyase and tryptophan indole-lyase are two PLP-dependent enzymes that catalyze the hydrolytic cleavage of tyrosine or tryptophan to phenol or indole, respectively, and ammonium pyruvate. Although the amino acid sequences and three dimensional structures are very similar, these enzyme are specific for their physiological substrates. We are determining the chemical mechanisms of both enzymes by synthesis of substrate and transition state analogs, steady state and rapid-scanning stopped-flow kinetics, and by using site-directed mutagenesis. We are also altering the substrate specificity by mutagenesis to identify the amino acids which determine the reaction specificity. Recently, we have determined the crystal structres of kynureninases from bacteria and human, and we are determining the structural basis for the differences in reaction specificity. We are studying a thermostable secondary alcohol dehydrogenase (SADH) isolated from a thermophilic bacterium. We demonstrated a novel temperature dependent reversal of stereospecificity of SADH in the reaction of 2-butanol. We are investigating a mutant SADH with specificity for aromatic substrates.
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Publications
"Differential Effects of Bromination on Substrates and Inhibitors of Kynureninase from Pseudomonas fluorescens" Heiss, C., Anderson, J. and Phillips, R. S., Org. Biomol. Chem., 1, 288-295 (2003).
"The Three Dimensional Structure of Kynureninase from Pseudomonas fluorescens" Momany, C., Levdikov, V., Blagova, L., and Phillips, R. S. Biochemistry, 43, 1193-1203 (2004).
"Hydrostatic Pressure Stabilizes the Open Conformation of Salmonella typhimurium Tryptophan Synthase" Phillips, R. S., Miles, E. W., Holtermann G., and Goody, R. S., Biochemistry, 44, 7921-7928 (2005).