Dietrich Professor

Research Interests   Protein Design, Structure and Function, and X-Ray Crystallography

Using mutagenesis to produce altered amino acid sequences and x-ray crystallography to study the resultant molecular structures, my objective is to formulate relationships explaining the biological, chemical and physical properties of a number of proteins which fall into several categories:

• proteins which interact with lipids.
• Enzymes which comprise the energy producing Kreb's cycle.
• Mitochondrial precursor proteins.
• An allosteric protein which is regulated by changes in Vmax.

To establish these structure/function relationships, x-ray studies are carried out on crystalline forms of the macromolecule. In the past, we have focussed on the purification and crystallization of proteins from their original biological sources, but now, using cloning and fermentation techniques, nearly all of the specimens for x-ray diffraction analyses are obtained from microbial sources containing the appropriate plasmid DNA. With the availability of structures from recombinant proteins, we are in a position to design new molecular forms. As an example, one graduate project focuses on changing a fatty acid binding protein into a retinoic acid binding protein. In the enzyme area, another project is aimed at determining the conformational changes occurring in a single domain of an enzyme regulated by serine.

In terms of graduate training, the x-ray crystallographic analyses have biophysical and computational aspects while the preparation of specimens and mutants requires experience in biochemistry and molecular biology. Students also train in the use of computer graphics to analyze structural data derived from both x-ray and NMR studies.

Thompson, J., Bell, J., Grant, G., and Banaszak, L., (2005), "Vmax regulation through domain and subunit changes. The active form of phosphoglycerate dehydrogenase", Biochemistry 44, 5763-5773.

Cox, B., Chit, M., Weaver,T., Gietl, C., Bailey, J., Bell, E. and Banaszak, L., (2005) "Organelle and translocatable forms of glyoxysomal malate dehydrogenase. The effect of the N-terminal presequence", FEBS Journal (formally: E.J.Biochem.) 272, 643-654.

Bell, J., Grant, G. and Banaszak, L. (2004) "Multi-conformational states in phosphoglycerate dehydrogenase", Biochemistry 43, 3450-3458.

Mariya Farooqui, Peter Franco, Jim Thompson, Hiroyuki Kagechika, Roshantha A.S. Chandraratna, Len Banaszak and Li-Na Wei (2003) "Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity " Biochemistry 42, 971-979.

Amy Reese and Leonard Banaszak, (2003) "Specificity determinants for lipids bound to b-barrel proteins", J. of Lipid Res. 45, 232-243.

Marcel Estevéz, Jeremy Skarda, Josh Spencer, Leonard Banaszak, and Todd M. Weaver, (2002) "Conformer Inactivation of Fumarase C from Escherichia coli", Prot Sci . 11, 1552-1557.

James Thompson and Leonard Banaszak, (2002) "Lipid-Protein interactions in lipovitellin", Biochemistry 41, 9398-9409.

Thompson, J., Bell, J., Grant, G., and Banaszak, L., (2005), "Vmax regulation through domain and subunit changes. The active form of phosphoglycerate dehydrogenase", Biochemistry (Web release date 25-Mar-05).