Faculty and Staff
Professor and Director, Biochemistry ProgramOffice: Chem 311A
Tuesdays and Thursdays 3:00 to 4:00 pm or by appointment
(Office entrance is through Chem 310)
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.
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.
McClelland, L. J., and Bowler, B. E. (2016) Lower protein stability does not necessarily increase local dynamics. Biochemistry 55, 2681–2693, doi:10.1021/acs.biochem.5b01060.
Goldes, M. E., Jeakins-Cooley, M. E. McClelland, L. J., Mou, T.-C., and Bowler, B. E. (2016) Disruption of a hydrogen bond network in human versus spider monkey cytochrome c affects heme crevice stability. J. Inorg. Biochem. 158, 62-69, doi:10.1016/j.jinorgbio.2015.12.025
Stine, J. M., Sun, Y., Armstrong, G., Bowler, B. E., and Briknarová. K. (2015) Structure and Unfolding of the Third Type III Domain from Human Fibronectin. Biochemistry 54, 6724–6733.
McClelland, L. J., Seagraves, S. M, Khan, Md K. A., Cherney, M. M., Bandi, S., Culbertson, J. E. and Bowler, B. E. (2015) The response of Ω-loop D dynamics to truncation of trimethyllysine 72 of yeast iso-1-cytochrome c depends on the nature of loop deformation. J. Biol. Inorg. Chem. 20, 805-819. doi:10.1007/s00775-015-1267-1
Bandi, S., and Bowler, B. E., (2015) Effect of an Ala81His mutation on the Met80 loop dynamics of iso-1-Cytochrome c, Biochemistry 54, 1729-1742. doi:10.1021/bi501252z
McClelland, L. J., Mou, T. C., Jeakins-Cooley, M. E., Sprang, S. R. and Bowler, B. E. (2014) Structure of a mitochondrial cytochrome c conformer competent for peroxidase activity, Proc. Natl. Acad. Sci. USA 111, 6648-6653. doi:10.1073/pnas.1323828111
Cherney, M. M., Junior, C. C. and Bowler, B. E. (2013). Mutation of trimethyllysine-72 to alanine enhances His79-heme mediated dynamics of iso-1-cytochrome c. Biochemistry 52, 837-846. doi:10.1021/bi301599g
Bandi, S. and Bowler, B. E. (2013). A cytochrome c electron transfer switch modulated by heme ligation and isomerization of a peptidyl-prolyl bond. Biopolymers, Peptide Science 100, 114-124. doi:10.1002/bip.22164/abstract
Khan, Md. K. A. and Bowler, B. E. (2012). Conformational properties of polyglutamine sequences in guanidine hydrochloride solutions. Biophys. J. 103, 1989-1999. doi:10.1016/j.bpj.2012.09.041
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.