James C. Powers Regents' Professor Emeritus Office: 3308 IBB Phone: 404-894-4038 Fax: 404-894-7452 E-mail James C. Powers Research Group Web site

B.S., Wayne State University, 1959; Ph.D., Massachusetts Institute of Technology, 1963; Special NIH Fellow, University of Washington, 1967.

Georgia Section ACS Herty Medal - 2000; Georgia Tech Distinguished Professor, Highest Academic Award -1999

Research Interests

Dr. Powers is interested in the study of enzyme active sites and the mechanism of enzyme catalysis. New classes of synthetic inhibitors are being designed and synthesized for proteolytic (protein degrading) enzymes of therapeutic importance. Both mechanism-based (or suicide) and transition-state inhibitors are being developed. One area of active research is the design and synthesis of inhibitors for proteases such as caspases and calpain. Inhibitors for calpain, a cysteine protease involved in neurodegeneration, have potential therapeutic utility for the treatment of stroke, Alzheimer's disease, and peripheral neuropathy. Inhibitors for caspases and related cysteine proteases have potential for the treatment of stroke, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinal muscular atrophy, inflammation, periodontal disease, parasite infection, and cancer. Both mechanism-based (or suicide) and transition-state inhibitors are being developed. Other research is concerned with elucidating the role of serine proteases (granzymes) and dipeptidyl peptidase I, which function in the killing of both virally infected cells and tumor cells by natural killer cells and cytotoxic T-lymphocytes.

Selected Publications

Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors-Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases), Ovat, A. Muindi, F., Fagan, C., Brouner, M., Hansell, E., Dvorak, J., Sojka, D., Kopacek, P., McKerrow, J., H., Caffrey, C. R., and Powers, J. C. (2009), J. Med. Chem. 52, 7192-7210.

Substrate Specificity of Transthyretin: Identification of Natural Substrates in the Nervous System, Liz, M. A., Fleming, C. E., Nunes, A. F., Almeida, M. R., Mar, R. M., Choe, Y., Craik, C. S., Powers, J. C., Bogyo, M., and Sousa, M. M. (2009) Biochemical J. 467-474.

Mechanistic and Structural Insights into the Proteolytic Activation of Vibrio cholerae MARTX Toxin, Shen, A., Lupardus, P. J., Albrow, V. E., Guzzetta, A., Powers, J. C., Garcia, K. C. and Bogyo, M. (2009) Nature Chemical Biology 5, 469-478.

Cocrystal Structures of Primed Side-Extending a-Ketoamide Inhibitors Reveal Novel Calpain-Inhibitor Aromatic Interactions, Qian, J., Cuerrier, D., Davies, P. L., Li, Z., Powers, J. C. and Campbell, R. L. (2008) J. Med. Chem. 51, 5264-5270.

Aza-Peptidyl Michael Acceptors – A New Class of Potent and Selective Inhibitors of Asparaginyl Endopeptidases (Legumains) from Evolutionarily Diverse Pathogens, Götz, M. G., James, K. E., Hansell, E., Dvořák, J., Seshaadri, A., Sojka, D., Kopáček, P., McKerrow, J. H., Caffrey, C. R. and Powers, J. C. (2008) J. Med. Chem. 51, 2816-2832.

Identification of Proteases that Regulate Erythrocyte Rupture by the Malaria Parasite Plasmodium falciparum, Arastu-Kapur, S., Ponder, E. L., Fonovi, U. P., Yeoh, S., Yuan, F., Fonovi, M., Grainger, M., Phillips, C. I., Powers, J. C., and Bogyo, M. (2008) Nature Chemical Biology 4, 203-213.

MHP-133, a Drug with Multiple CNS Targets: Potential for Neuroprotection and Enhanced Cognition, Buccafusco, J. J., Powers, J. C., Hernandez, M. A., Pendergast, M. A., Terry, A. V., and Jonnala, R. R. (2007) Neurochem. Res. 32, 1224-1237.

Crystal Structures Reveal an Induced-fit Binding of a Substrate-like Aza-Peptide Epoxide to SARS Coronavirus Main Peptidase, Lee, T-W., Cherney, M. M., Liu, J., James, K. E., Powers, J. C.,  Eltis, L. D., and James, M. N. G. (2007) J. Mol. Biol. 366, 916-32.

Design, Synthesis, and Evaluation of Aza-Peptide Michael Acceptors as Selective and Potent Inhibitors of Caspases-2, -3, -6, -7, -8, -9, and -10, Ekici, O. D., Li, Z. Z., Campbell, A. J., James, K. E., Asgian, J. L., Mikolajczyk, J., Salvesen, G. S., Ganesan, R., Jelakovic, S., Grütter, M. G. and Powers, J. C. (2006) Biochemistry 49, 5728-5749.

Exploring the S4 and S1 Prime Subsite Specificities in Caspase-3 with Aza-Peptide Epoxide Inhibitors, Ganesan, R., Jelakovic, S., Campbell, A. J., Li, Z. Z., Asgian, J. L., Powers, J. C. and Grütter, M. G. (2006) Biochemistry 45, 9059-9067.

Crystal Structures of the Main Protease from the SARS Coronavirus Inhibited By A Substrate-Like Aza-Peptide Epoxide, Lee, T-W., Cherney, M. M., Huitema, C, Liu, J., James, K. E., Powers, J. C., Eltis, L.  D., and James, M. N. G. (2005) J. Mol. Biol. 353, 1137-1151.

Fluorescently labeled inhibitors detect localized serine protease activities in Drosopilia melangaster pole cells, embryos, and ovarian egg chambers, Jakobsen, R. K., Ono, S., Powers, J. C., and DeLotto, R. (2005) Histochem. Cell Biol. 123, 51-60.