Ñý¼§Ö±²¥

Personal Summary

Bruce Bowler joined the Ñý¼§Ö±²¥ 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 Center for Biomolecular Structure and Dynamics.

Education

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

Courses Taught

Research Interests

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 cytochrome 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.

Selected Publications

Lei, H., Kelly, A. D., and Bowler, B. E. (2022) Alkaline state of the domain-swapped dimer of human cytochrome c: a conformational switch for apoptotic peroxidase activity, J. Am. Chem. Soc. 144, 21184-21195, .

Frederick, A. K., Thompson, S. L., Vakharia, Z. M., Cherney, M. M., Lei, H., Evenson, G., and Bowler, B. E. (2022) Effect on intrinsic peroxidase activity of substituting coevolved residues from Ω-loop C of human cytochrome c into yeast iso-1-cytochrome c, J. Inorg. Biochem. 232, 111819, .

Becht, D. C., Leavens, M. J., Zeng, B., Rothfuss, M. T., Briknarová, K., and Bowler, B. E. (2022) Residual structure in the denatured state of the fast-folding UBA(1) domain from the human DNA excision repair protein HHR23A, Biochemistry 61, 767–784, .

Leavens, M. J., Spang, L. E., Cherney, M. M., and Bowler, B. E. (2021) Denatured state conformational biases in three-helix bundles containing divergent sequences localize near turns and helix capping residues, Biochemistry 60, 3071−3085, .

Steele, H. B. B., Elmer-Dixon, M. M., Rogan, J. T., Ross, J. B. A., and Bowler, B. E. (2020) The human cytochrome c domain-swapped dimer facilitates tight regulation of intrinsic apoptosis, Biochemistry 59, 2055-2068, .

Elmer-Dixon, M. M., Xie, Z., Alverson, J. B., Priestley, N. D., and Bowler, B. E. (2020) Curvature dependent binding of cytochrome c to cardiolipin, J. Am. Chem. Soc. 142, 19532-19539, .

Elmer-Dixon, M. M., Hoody, J. Steele, H. B. B., Becht, D. C., and Bowler, B. E. (2019) Cardiolipin preferentially partitions to the inner leaflet of mixed lipid large unilamellar vesicles, J. Phys. Chem. B 123, 9111–9122, .

Lei, H., and Bowler, B. E. (2019) The naturally occurring A51V variant of human cytochrome c destabilizes the native state and enhances peroxidase activity, J. Phys. Chem. B 123, 8939−8953,.

Lei, H., Nold, S. M., Jung Motta, L., and Bowler, B. E. (2019) Effect of V83G and I81A substitutions to human cytochrome c on acid unfolding and peroxidase activity below neutral pH, Biochemistry 58, 2921−2933, .

Elmer-Dixon, M. M., and Bowler, B. E. (2018) Electrostatic constituents of cardiolipin interaction with site A of cytochrome c, Biochemistry 57, 5683−5695, .

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,

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,

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,

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,

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,

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,

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,

Elmer-Dixon, M. M., and Bowler, B. E. (2017) Rapid quantification of cardiolipin and DOPC lipid and vesicle concentration. Anal. Biochem. 520, 58-61,

Publications