Assistant Professor of Biochemistry
B.S. (Chemistry), Stetson University, 1989
Ph.D. (Biochemistry and Molecular Biology) University of Florida (B.M. Dunn), 1994
Postdoctoral (Protein Crystallography) Institute of Molecular Biology, University of Oregon (B.W. Matthews)
Phone: (336) 716-7230
E-mail: tlowther@wfubmc.edu
The overall focus of several ongoing projects in my laboratory is to understand the molecular basis for enzyme catalysis and substrate/inhibitor/ligand specificity. In these endeavors we utilize a variety of molecular biology, biochemical and X-ray crystallographic methods. Current projects in the lab include: (1) an analysis of the molecular basis for the repair or retro-reduction of hyperoxidized peroxiredoxins by an enzyme called surfiredoxin, (2) the characterization of enzymes involved in glyoxylate metabolism and kidney stone formation, (3) the study of the thioesterase domain of human fatty acid synthase and its inhibition by the anti-cancer compound Orlistat, and (4) the study of methionine sulfoxide reductases.
Selected Publications
Sulfiredoxin-Peroxiredoxin Interactions:
Sulfiredoxin/Peroxiredoxin catalytic cycles and the Srx-Prx complex
Jönsson, T.J., Johnson, L.C., and Lowther W.T. (2008) Structure of the sulphiredoxin-peroxiredoxin complex reveals an essential embrace for repair, Nature 451:98-101. PDF
Jönsson, T.J. and Lowther, W.T. (2007). The peroxiredoxin repair proteins. in Peroxiredoxin Systems: Structures and Functions, L. Flohé and J.R. Harris, eds., Springer, 115-141, ISBN: 978-1-4020-6050-2.
Jönsson, T.J., Murray, M.S., Johnson, L.C., Poole, L.B., and Lowther, W.T. (2005). Structural basis for the retroreduction of inactivated peroxiredoxins by human sulfiredoxin. Biochemistry 44, 8634-8642. PDF
Characterization of Enzymes Involved in Glyoxylate Metabolism and Kidney Stone Formation
Murray, M.S., Holmes, R.P. and Lowther, W.T. (2008) Active stie and loop 4 movements withing human glycolate oxidase: implications for substrate specificity and drug design, Biochemistry, in press.
Targeting the Thioesterase Domain of Human Fatty Acid Synthase for Cancer Therapy:
Crystal structure of the FAS-TE-Orlistat complex
Pemble, IV, C.W., Johnson, L.C., Kridel, S.K., and Lowther, W.T. (2007) Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat, Nature Struct. Mol. Biol. 14:704-709. PDF
Methionine Sulfoxide Reductases:
Escherichia coli free Met-R(O) reductase structure and function
Lin, Z., Johnson, L.C., Weissbach, H., Brot, N., Lively, M.O., and Lowther, W.T. (2007) Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function. Proc. Natl. Acad. Sci. U.S.A. 104:9597-9602. PDF
Brot, N., Collet, J., Johnson, L.C., Jönsson, T.J., Weissbach, H., and Lowther, W.T. (2006). The thioredoxin domain of Neisseria gonorrhoeae PilB can use electrons from DsbD to reduce downstream methionine sulfoxide reductases. J. Biol. Chem. 281: 32668-32675. PDF
Lowther, W.T., Weissbach, H., Etienne, F., Brot, N. and Matthews, B.W. (2002). The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB. Nature Struct. Biol. 9, 348-352. PDF
Lowther, W.T., Brot, N., Weissbach, H. and Matthews, B.W. (2000). Structure and mechanism of peptide methionine sulfoxide reductase, an "anti-oxidation" enzyme. Biochemistry 39, 13307-13312. PDF
Lowther, W.T., Brot, N., Weissbach, H., Honek, J.F. and Matthews, B.W. (2000). Thiol-disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase. Proc. Natl. Acad. Sci. U.S.A. 97, 6463-6468. PDF
Current Laboratory Members
Graduate Students: Charles Pemble, Michael Murray
Postdoctoral Fellow: Dr. Thomas Jonsson
Technicians: Lynnette Johnson and Dana Jasso