Faculty

A major health problem today is an increasing resistance in pathogenic bacteria to the classic antibacterials, such as the penicillins. A potential approach to overcoming this problem is to design new and innovative agents with a totally different mode of action; therefore, no cross-resistance with present therapeuticals should occur. Many pharmacologically important drugs act by inhibiting key enzymes in various primary and secondary biochemical cascades. To be successful in this approach one needs a thorough understanding of the enzyme(s) at the molecular level.

The goal of our group is to use mechanistic information obtained from substrate analogue studies, in parallel with studies utilizing regio- and stereo-specifically labeled substrates and information from kinetic methodologies, in the design and synthesis of selective enzyme inhibitors of pivotal enzymes in critical biosynthetic cascades.

Awards

Fellow of the American Association for the Advancement of Science

Representative Publications

1. Wu, J. and Woodard,R.W., "YrbI is the Specific 3-Deoxy-D- manno -Octulosonate 8-Phosphate Phosphatase in Escherichia coli", J. Biol. Chem., 2003, 278, 18117-18123.

2. Howe, D.L., Sundaram, A.K., Gatti, D.L. and Woodard, R.W., "Mechanistic Insight into 3-deoxy-D-manno-octilosonate-8-phosphate Synthase (KDO8-P Synthase) and 3-deoxy-D-arabino-heptulosonate-7-phosphate Synthase (DAH7-P Synthase) Utilizing Phosphorylated Monosaccharide Analogues", Biochem., 2003, 42, 4843-4845.

3. Wu, J., Howe, D.L. and Woodard, R.W., "Thermotoga maritima 3-Deoxy-D-arabino-heptulosonate 7-phosphate Synthase: The Ancestral Eubacterial DAHP Synthase?", J. Biol. Chem., 2003, 278, 27525-27531.

4. Merideth, T. and Woodard, R.W., "Escherichia coli YrbH is a D-Arabinose 5-phosphate Isomerase", J. Biol. Chem., 2003, 278, 32771-32777.

5. Li, J., Wu, J., Fleischhacker, A.S. and Woodard, R.W., "Conversion of Aquifex aeolicus 3-Deoxy-D-manno-octulosonate 8-phosphate Synthase, a Metalloenzyme, into a Non-metalloenzyme", J. Am. Chem. Soc., 2004, 126, 7448-7449.

6. Shumilin, I.A., Bauerle, R., Wu, J, Woodard, R.W. and Kretsinger, R.H., "Crystal structure of the reaction complex of 3-deoxy-D-arabino-htptulosonate-7-phosphate synthase from Thermotoga maritima refines the catalytic mechanism and indicates a new mechanism of allosteric regulation", J. Mol. Biol., 2004, 341, 455-466.