Bruce Bowler - Professor of Chemistry
Office Location: Chem 311A
Office Telephone: 406-243-6114
Bruce Bowler joined the University of Montana in 2006 as Professor of Chemistry and a member of the Center for Biomolecular Structure and Dynamics. He received his Ph. D. degree in 1986 with Stephen J. Lippard at the Massachusetts Institute of Technology. From 1986 to 1989, he was a Medical Research Council of Canada postdoctoral fellow in the laboratories of Harry Gray and Jack Richards at the California Institute of Technology. From 1989 to 2006 he was a professor of chemistry at the University of Denver. Dr. Bowler is a physical biochemist with interests in protein folding and biological electron transfer reactions. Dr. Bowler is also the Director of the newly developed Biochemistry Program. Information for that program may be found at http://www.cas.umt.edu/biomolecular/.
Research in the Bowler lab focuses on two areas: protein folding and electron transfer reactions in proteins and peptides. Currently, work on protein folding centers on understanding the conformational properties of denatured states that provide for efficient folding and on the molecular basis of the cooperative stability of proteins. Insight into these aspects of protein folding will shed light on the causes of protein misfolding and aggregation which can lead to pathological conditions such as Alzheimer’s disease and cystic fibrosis.
Electron transfer reactions involving proteins are essential to the metabolism of all living organisms and are particularly important in photosynthesis in plants and energy storage in animals. We are interested in understanding how the protein matrix, particularly hydrogen bond networks, modulates the rates of electron transfer reactions. We are also exploiting protein conformational changes as a means of creating molecular switches that can turn electron flow on and off and ultimately be used as components of molecular electronics devices.
The Bowler lab uses site-directed mutagenesis as a tool to create protein variants for these studies. We then characterize the thermodynamic and structural properties of these variants using electronic, fluorescence, circular dichroism, NMR and mass spectroscopies. The kinetic and dynamic properties of these variants are probed using stopped and continuous flow methods and limited proteolysis techniques.
Khan, Md. K. A., Miller, A. L. and Bowler, B. E. (2012). Tryptophan stabilizes His-heme loops in the denatured state only when it is near a loop end. Biochemistry, in press doi:10.1021/bi300212a.
Finnegan, M. L. and Bowler, B. E. (2012). Scaling properties of glycine-rich sequences in guanidine hydrochloride solutions. Biophysical J. 102, 1969-1978. doi:10.1016/j.bpj.2012.03.049
Bowler, B. E. (2012) Characterization of the denatured state. In Egelman, E. H, editor: Comprehensive Biophysics Vol 3, The folding of Proteins and Nucleic Acids, Daggett, V., volume editor, Oxford: Academic Press, pp. 72-114.
Bowler, B. E. (2012). Residual structure in unfolded proteins. Curr. Opin. Struct. Biol. 22, 4-13. doi:10.1016/j.sbi.2011.09.002
Bandi, S. and Bowler B. E.; (2011). Probing the dynamics of a His73-heme alkaline transition in a destabilized variant of yeast iso-1-cytochrome c with conformationally gated electron transfer. Biochemistry 50, 10027–10040. doi:10.1021/bi201082h
Cherney, M. M.; Bowler, B. E. (2011) Protein dynamics and function: making new strides with an old warhorse, the alkaline conformational transition of cytochrome c. Coord. Chem. Rev. 255, 664-677. doi:10.1016/j.ccr.2010.09.014
Dar, T. A., Schaeffer, R. D., Daggett, V. and Bowler, B. E. (2011) Manifestations of native topology in the denatured state ensemble of Rhodopseudomonas palustris cytochrome c’. Biochemistry 50, 1029-1041. doi:10.1021/bi101551h
Finnegan, M. L. and Bowler, B. E. (2010). Propensities of aromatic amino acids versus leucine and proline to induce residual structure in the denatured state ensemble of iso-1-cytochrome c. J. Mol. Biol. 493, 495-504 doi:10.1016/j.jmb.2010.09.004.
Tzul, F. O. and Bowler, B. E. (2010). Denatured states of low complexity polypeptide sequences differ dramatically from those of foldable sequences. Proc. Natl. Acad. Sci. U.S.A.107, 11364-11369 doi:10.1073/pnas.1004572107.
Rao, K. S., Tzul, F. O., Christian, A. K, Gordon, T. N. and Bowler, B. E. (2009). Thermodynamics of loop formation in the denatured state of Rhodopseudomonas palustris cytochrome c': scaling exponents and the reconciliation problem. J. Mol. Biol. 392, 1315-1325. doi:10.1016/j.jmb.2009.07.074
Tzul, F. O., and Bowler, B. E. (2009). Importance of contact persistence in denatured state loop formation: kinetic insights into sequence effects on nucleation early in folding. J. Mol. Biol. 390, 124-134. doi:10.1016/j.jmb.2009.04.075
Duncan, M. G., Williams, M. D., and Bowler, B. E. (2009). Compressing the free energy range of substructure stabilities in iso-1-cytochrome c. Protein Sci. 18, 1155-1164. doi:10.1002/pro.120
Tzul, F. O., Kurchan, E., Roder, H. and Bowler, B. E. (2009). Competition between reversible aggregation and loop formation in denatured iso-1-cytochrome c. Biochemistry 48, 481-491 doi:10.1021/bi801977j
Bandi, S., and Bowler, B. E. (2008). Probing the bottom of a folding funnel using conformationally gated electron transfer reactions. J. Am. Chem. Soc. 130, 7540-7541. doi:10.1021/ja801941r