|BS||University of Missouri||Columbia, Mo.||Chemistry|
|PhD||Brown University||Providence, R.I.||Chemistry|
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.
Substrate channeling in proline catabolic enzymes. This project is supported by NIH grant R01GM065546.
Functional switching in proline metabolism. This project is funded by NIH grant R01GM061068.
Structural studies of UDP-galactopyranose mutase, a novel target for the design of anti-fungal drugs and drugs to treat tropical neglected diseases.
This project is supported by NIH grant R01GM094469.
Boechi L, de Oliveira CA, Da Fonseca I, Kizjakina K, Sobrado P, Tanner JJ, McCammon JA. Substrate-dependent dynamics of UDP-galactopyranose mutase: Implications for drug design. Protein Sci. (2013).
T.A. Pemberton and J.J. Tanner Structural basis of substrate selectivity of Δ1-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): Semialdehyde chain length. Arch. Biochem. Biophys. (2013) Accepted.
Min Luo, R.K. Singh, and J.J. Tanner Structural Determinants of Oligomerization of 1-Pyrroline-5-Carboxylate Dehydrogenase: Identification of a Hexamerization Hot Spot. J. Mol. Biol. 425(17):3106-3120 (2013).
Zhu W, Haile AM, Singh R, Larson JD, Smithen D, Chan JY, Tanner JJ, Becker DF. Involvement of the β3-α3 loop of the Proline Dehydrogenase Domain in Allosteric Regulation of Membrane Association of Proline Utilization A. Biochemistry 52(26):4482-9 (2013).
K. Kizjakina, J. J. Tanner, and P. Sobrado Targeting UDP-Galactopyranose Mutases from Eukaryotic Human Pathogens. Current Pharmaceutical Design 19(14):2561-73 (2013).