David A.R. Sanders Associate Professor of Chemistry Protein X-Ray Crystallography and Enzymology B.Sc. (Hons. Biochemistry Co-Op) : Guelph 1991 Ph.D., University of Arizona 1998 Post-Doc : St. Andrews University, Scotland 1998-2001 Office: Thorvaldson 153 Phone: (306) 966-6788 E-mail: david.sanders@usask.ca Website: http://prospero.usask.ca/

Research Interests

Work in my lab focuses on studying molecular structure and function using Protein X-ray crystallography and Enzymology and other biochemical and biophysical approaches. Two projects are currently underway, with possibilities of more being discussed :

1. Mechanism of UDP-galactopyranose mutase (mutase): This enzyme is a potential drug target for pathogenic organisms. Mutase is responsible for the interconversion of the 6-membered ring UDP-Galp and the 5-membered ring UDP-Galf. UDP-Galf is the precursor of Galf and is an important component of bacterial (and other pathogens) cell walls. The enzyme is novel and the mechanism is not understood. We plan to solve the structures of mutase from different organisms, with and without potential inhibitors in order to help determine the mechanism. Site-directed mutagenesis will also be employed to aid in these determinations. This project involves molecular biology, enzymology and crystallography.
2. Interaction between Thioredoxin (Trx) and NFkappaB (NFkB) : NFkB is an important activator of transcription, and studies have shown that among other ways, NFkB activity can be enhanced by interaction with the redox protein thioredoxin. This project will characterize the interaction between Trx and NFkB using crystallography and biophysical approaches. Once the interaction is characterized fully, mutants will be constructed to study the physiological role of this interaction.

Additional projects are being discussed with other members of the University, from the Departments of Chemistry, Biochemistry, Biology, Plant Science and Microbiology.

Representative Publications

• Karunan Partha, S., van Straaten, K.E. and Sanders, D.A.R. (2009) Structural Basis of Substrate Binding to UDP-Galactopyranose Mutase: Crystal Structures in the Reduced and Oxidized State Complexed with UDP-Galactopyranose and UDP. J. Mol. Biol., 394:864-877.
• van Straaten, K.E., Gonzalez, C.F., Valladares, R.B., Xu, X., Savchenko, A.V. and Sanders, D.A.R. (2009) The Structure of a Putative S-Formylglutathione Hydrolase from Agrobacterium tumefaciens. Prot. Sci., 18 :2196-2202.
• El-Ganiny, A.M., Sanders, D.A.R., and Kaminskyj, S.G.W.* (2008) Aspergillus nidulans UDP-Galactopyranose Mutase, Encoded by ugmA Plays Key Roles in Colony Growth, Hyphal Morphogenesis, and Conidiation. Fun. Gen. Biol., 45:1533-1542.
• Chad, J.M., Sarathy, K.P., Gruber, T.D., Addala, E., Kiessling, L.L., and Sanders, D.A.R.* (2007) Site-Directed Mutagenesis of UDP-Galactopyranose Mutase Reveals a Critical Role for the Active-Site, Conserved Arginine Residues. Biochemistry, 46: 6723-6732.