Faculty: Biography

Robert S. Phillips, Ph.D.
Professor
Chemistry
Address: Chemistry Building
University of Georgia
Athens, GA 30602
Office: Room 511
Phone: (706) 542-1996
Email: rsphillips@chem.uga.edu
Biosketch
B.S. ChemistryGeorgia Institute of TechnologyAtlanta, GA1974
Ph.D. ChemistryGeorgia Institute of TechnologyAtlanta, GA1979
Post-doctoral Experience
Post-doctoral, Enzyme Mechanisms, Chemistry Department, Georgia Institute of Technology, 1979-1980
Post-doctoral, Enzyme Regulation, National Institute of Mental Health, 1981-1983
Honors and Awards
Japan Society for the Promotion of Science Fellowship, 1992
Northeast Georgia Section, American Chemical Society
Chemist of the Year for Research, 1992
Northeast Georgia Section, American Chemical Society
Chemist of the Year for Service, 1995
Creative Research Medal, University of Georgia Research Foundation, 1996
Dozor Visiting Professor, Ben-Gurion University, Beersheeva, Israel, 1997
Ad Hoc member, Biochemistry Study Section, National Institutes of Health, February 22-23,2001
Ad Hoc member, Biochemistry Study Section, National Institutes of Health, February 21-22, 2002
Research Interests
Enzymes are remarkable biocatalysts, not only for the dramatic rate accelerations (up to 1020 fold) that they provide, but also for the high degree of substrate specificity, regiospecificity and stereospecificity that these reactions exhibit. Work 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 of the two enzymes 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. Another PLP-dependent enzyme being studied in my laboratory is kynureninase. We have cloned this enzyme from Pseudomonas fluorescens and Homo sapiens and we have studied the mechanism by steady state and pre-steady state kinetic methods. Recently, we have determined the crystal structures of bacterial and human kynureninases, and we are determining the structural basis for the differences in reaction specificity. We have also synthesized potent mechanism based inhibitors of kynureninase that could be useful as drugs. In other work, 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 currently investigating a mutant SADH with specificity for aromatic substrates. (This research is partially supported by a grant from the National Institutes of Health and the National Science Foundation.)
Representative Publications
“Detection of Open and Closed Conformations of Tryptophan Synthase by 15N-HSQC NMR of Bound 1-15N-L-Tryptophan”, Osborne, A., Teng , Q., Miles, E. W., and Phillips, R. S., J. Biol. Chem., 278, 44083-44090 (2003).

“Histidine Ligand Protonation and Redox Potential in the Rieske Dioxygenases: Role of a Conserved Aspartate in Anthranilate 1,2- Dioxygenase”, Beharry, Z. M., Eby, D. M., Coulter, E. D., Viswanathan, R., Neidle, E. L., Phillips, R. S. and Kurtz, D. M., Jr., Biochemistry,42,13625-13636 (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).

“Functional Characterization of Tyrosine Phenol-lyase and Tyrptophan Indole-lyase Encapsulated in Wet Nanoporous Silica Gels”, Pioselli, B., Demidkina, T., Phillips, R. S. and Mozzarelli, A., Protein Science, 13, 913-924 (2004).

“Reaction of b-Benzoyl-L-alanine with Kynureninase from Pseudomonas fluorescens: Detection of a New Reaction Intermediate and a Change in Rate-determining Step”, Gawandi, V., Liskey, D., Lima, S., and Phillips, R. S., Biochemistry, 43, 3230-7 (2004).
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