Robert S. Phillips Professor of Chemistry and Biochemistry & Molecular Biology Professor Phillips received his B. S. in 1974 and his Ph. D. in 1979 from the Georgia Institute of Technology. He was a Staff Fellow in the Laboratory of Neurochemistry at the National Institute of Mental Health from 1980-1982, and was Senior Staff Fellow in the Laboratory of Bioorganic Chemistry at the National Institute for Arthritis, Diabetes, Digestive and Kidney Diseases from 1982-1985, before joining the Georgia faculty in 1985. Research in our group is directed toward understanding the ways in which enzymes achieve their enormous catalytic rate enhancements. We are studying the relationship between structure and stereochemistry in a Zn-containing secondary alcohol dehydrogenase (SADH) from a thermophilic anaerobic bacterium, Thermoanaerobacter ethanolicus. Our work has demonstrated the first temperature-dependent inversion of stereochemistry in an enzyme-catalyzed reaction in this system. We are now examining the effects of metal substitution and mutation of active site residues on the stereochemical course of SADH reactions. These results will provide important new information on the recognition of stereoisomers in enzymatic reactions. An exciting area of research that we are now pursuing is in monovalent cation-dependent enzymes. Many enzymes are now known to require K + for activity, but the role of the monovalent cation in catalysis is not well understood, as the binding is weak and the metal is spectroscopically silent. We have recently obtained an x-ray structure of a K +-dependent enzyme, tyrosine phenol-lyase, and we have located the cation binding site. We are now probing the role of the metal in the enzyme structure and mechanism by site-directed mutagenesis of the metal ligands. "The Role of Glutamic Acid-69 in the Activation of Citrobacter freundii Tyrosine Phenol-lyase by Monovalent Cations," Sundararaju, B.; Chen, H.; Shillcutt, S.; Phillips, R. S. Biochemistry. 2000, 39, 8546-8555. "The Stereospecificity of Secondary Alcohol Dehydrogenase from Thermoanaerobacter ethanolicus is Partially Determined by Active Site Water," Heiss, C.; Laivenieks, M.; Zeikus, J. G.; and Phillips, R. S. J. Am. Chem. Soc. 2001, 123, 345-346. "Mutation of Cysteine-295 to Alanine in Secondary Alcohol Dehydrogenase from Thermoanaerobacter ethanolicus Affects the Enantioselectivity and Substrate Specificity of Ketone Reductions," Heiss, C.; Laivenieks, M.; Zeikus, J. G.; and Phillips, R. S. Bioorg. Med. Chem. 2001, 9, 1659-1666. E-mail contact: rsphillips@sunchem.chem.uga.edu Website: http://tryptophan.net