Faculty and Staff
Professor and Director, Biochemistry ProgramOffice: Chem 311A
Tuesdays and Thursdays 11:00 am to noon 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, the conformational restraints that specify the protein folding code and protein dynamics as applied to the conformational changes that mediate the function of cytochrome c in apoptosis. Dr. Bowler is also the Director of the Biochemistry Program.
B.S. in Chemistry, Brown University, Providence, RI, 1981
M.S. in Chemistry, Columbia University, New York, NY, 1982
Ph.D. in Chemistry, MIT, Cambridge, MA, 1986
Postdoctoral Fellow, Chemistry, Caltech, Pasadena, CA, 1986-1989
Research in the Bowler lab focuses on two areas: protein folding and the relationship between protein conformational dynamics and function.
Our work on protein folding emphasizes the conformational biases inherent in protein denatured states that bias the free energy landscape of a protein toward its native conformer. The ultimate goal of this research is to understand the physical basis of the protein folding code.
Our work on the relationship between protein conformational dynamics and function focuses on the structural factors that control access to conformers of mitochondrial cytochrome c which permit peroxidase activity. Under conditions of oxidative stress cytochome c oxygenation of the inner mitochondrial membrane lipid, cardiolipin, provides the earliest signal in the intrinsic pathway of apoptosis. A key goal of this work is to understand how cytochrome c has evolved to become a regulatory on/off switch for apoptosis.
Elmer-Dixon, M. M., and Bowler, B. E. (2018) Electrostatic constituents of cardiolipin interaction with site A of cytochrome c, Biochemistry 57, 5683−5695, doi:10.1021/acs.biochem.8b00704.
Elmer-Dixon, M. M., and Bowler, B. E. (2018) Rapid quantification of vesicle concentration for DOPG/DOPC and cardiolipin/DOPC mixed systems of variable composition. Anal. Biochem. 553, 12-14, https://doi.org/10.1016/j.ab.2018.05.013
Lei, H. and Bowler, B. E. (2018) Humanlike substitutions to Ω-loop D of yeast iso-1-cytochrome c only modestly affect dynamics and peroxidase activity, J. Inorg. Biochem. 183, 146-156, https://doi.org/10.1016/j.jinorgbio.2018.02.022
Leavens, M. J., Cherney, M. M., Finnegan, M. L. and Bowler, B. E. (2018) Probing denatured state conformational bias in a three-helix bundle, UBA(2), using a cytochrome c fusion protein, Biochemistry 57, 1711−1721, doi:10.1021/acs.biochem.8b00015
Danielson, T. A. and Bowler, B. E. (2018) Helical propensity affects the conformational properties of the denatured state of cytochrome c′, Biophys. J. 114, 311–322, https://doi.org/10.1016/j.bpj.2017.11.3744
Danielson, T. A., Stine, J. M. Dar, T. A., Briknarova, K. and Bowler, B. E. (2017) Effect of an imposed contact on secondary structure in the denatured state of yeast iso-1-cytochrome c, Biochemistry 56, 6662−6676, doi:10.1021/acs.biochem.7b01002
Elmer-Dixon, M. M., and Bowler, B. E. (2017) Site A-mediated partial unfolding of cytochrome c on cardiolipin vesicles is species-dependent and does not require Lys72, Biochemistry 56, 4830−4839, doi:10.1021/acs.biochem.7b00694
Nold, S. M., Lei, H., Mou, T.-C., and Bowler, B. E. (2017) Effect of a K72A mutation on the structure, stability, dynamics and peroxidase activity of human cytochrome c, Biochemistry 56, 3358−3368, doi:10.1021/acs.biochem.7b00342
Elmer-Dixon, M. M., and Bowler, B. E. (2017) Rapid quantification of cardiolipin and DOPC lipid and vesicle concentration. Anal. Biochem. 520, 58-61, https://doi.org/10.1016/j.ab.2016.12.024
McClelland, L.J., Steele, H. B. B., Whitby, F. G., Mou, T.-C., Holley, D., Ross, J. B. A., Sprang, S. R., and Bowler, B. E. (2016) Cytochrome c can form a well-defined binding pocket for hydrocarbons. J. Am. Chem. Soc. 138, 16770−16778. doi:10.1021/jacs.6b10745
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