Education
| BS | Chemistry | University of Missouri | Columbia, Mo. |
| PhD | Chemistry | Brown University | Providence, R.I. |
Research Areas
X-ray crystallography of proline metabolic enzymes, bacterial virulence proteins and anti-DNA antibodies; structural bioinformatics of protein-bound water; molecular dynamics simulations of biological molecules.
Research Description
We study protein structure and its relationships to protein function at the molecular and cellular levels. The general term that is used for our brand of research is “structural biology”. Common to all of our work is a focus on understanding how biomolecules recognize and engage one another. Biomolecular recognition is important because virtually all of biological chemistry occurs when two or more molecules come together to effect a reaction or transmit a signal. For example, enzymes must recognize their natural substrates from the myriad of other molecules in living cells, while transcriptional repressors must recognize a specific DNA sequence to control gene expression.
We employ a variey of experimental and computational methods. Our main experimental tool is X-ray crystallography, which provides high resolution three-dimensional structures of proteins. High resolution structural information is indispensable for understanding how proteins function. For example, structures of enzymes with substrates or substrate-like compounds bound in the active site inform us about substrate recognition, which provides insight into the chemical mechanism. Furthermore, crystal structures of protein-ligand complexes facilitate the design of new enzyme inhibitors. Such inhibitors represent lead compounds for drug development, thus protein crystallography plays an important role in the early stages of drug discovery. We also supplement our crystallographic work with a variety of other approaches, including small-angle X-ray scattering (SAXS), site-directed mutagenesis, kinetics measurements, analytical ultracentrifugation, isothermal titration calorimetry, and a variety of computational methods.
Notable Honors and Service
Honors
- Faculty Fellow Award, University of Missouri Department of Biochemistry, 2017
- William Evans Fellowship, University of Otago, Dunedin, NZ, 2017
Editorial Board Member
- Journal of Biological Chemistry
- Archives of Biochemistry and Biophysics
NIH and NSF Grant Proposal Review Panels
- NIH MSFA Study Section, regular member, Washington and San Francisco, 2013-16
- NIH NIAID SEP on Centers for Structural Genomics for Infectious Diseases, 2016
- NIH ZRG1 BCMB-G (02) SEP, 2018
- NIH ZRG1 CB-B panel, MIRA R35 Outstanding Investigator Awards, Potomac, MD, 2018
- NSF Chemistry of Life Processes Enzyme Chemistry panel, Washington, DC, 2018
Other
- Chair-Elect, ACA Biological Macromolecules Scientific Interest Group, 2016
- Chair, ACA Biological Macromolecules Scientific Interest Group, 2017
- Co-Chair, Session on the Structural Biology of Inherited Metabolic Disorders, 2018 ACA national meeting in Toronto, CA, 2018
Selected Publications
Full list of publications here.
Current Funding
- COORDINATION OF FUNCTIONS BY PROLINE METABOLIC PROTEINS
- INHIBITION OF UDP-GALACTOPYRANOSE MUTASES FROM EUKARYOTIC PATHOGENS
- INTEGRATED PREDICTION AND VALIDATION OF PROTEIN STRUCTURES