Kara L. Bren

Kara L. Bren

Professor of Chemistry


Ph.D. 1996, California Institute of Technology

Bioinorganic and biophysical chemistry

Professor Bren's research interests lie in the fields of bioinorganic and biophysical chemistry. The Bren group is investigating structure, folding, dynamics, electronic structure, and function of heme proteins in the cytochrome c family. The heme chromophore serves as a valuable spectroscopic probe used in paramagnetic NMR, EPR, resonance Raman, and fluorescence energy transfer experiments. In addition, the Bren group uses a variety of biochemical techniques including site-directed mutagenesis and protein expression. Students taking part in this research have the opportunity to learn a wide range of approaches to a problem.

One major project involves the study of the molecular and electronic structure of the heme group in cytochrome c proteins. The heme in this protein family displays a wide range of structures (from planar to highly ruffled) and redox potentials (with a range of ~ 1 V). A goal of this project is to learn the relationship between structure and function of the heme and its ligating amino acids. As part of this project, the Bren group is developing new NMR methods for characterizing heme structure. The results obtained in this work will help us gain a more complete understanding of how nature controls electron transfer reactions.

The Bren group uses spectroscopy to investigate cytochrome c folding and dynamics.

In a project being done in collaboration with UR Professor Todd Krauss, the Bren group is employing optical methods to study protein folding using cytochrome c as a model system. A primary focus is to characterize the heterogeneity of protein folding by employing single-molecule spectroscopic methods. In addition, the Bren group is developing the use of zinc porphyrin as a fluorescent probe of folding and dynamics of proteins, including proteins that do not normally bind heme. Zinc porphyrin also is a convenient chromophore to utilize in solar energy conversion. In the group’s newest project, zinc porphyrin peptides are being prepared and tested for this application.

Selected Publications

Asher, W.B., Bren, K.L.  "Affinity Purification of Heme-tagged Proteins,"  Protein Affinity Tags: Methods and Protocols,  Springer (New York) 2014vol. 117717-33.
Sun, Y., Benabbas, A., Zeng, W., Kleingardner, J.G., Bren, K.L., Champion, P.M.  "Investigations of Heme Distortion, Low-Frequency Vibrational Excitations, and Electron Transfer in Cytochrome c,"  Proc. Natl. Acad. Sci. USA  20141116570-6575. http://dx.doi.org/10.1073/pnas.1322274111
Kleingardner, J.G., Kandemeir, B., Bren, K.L.  "Hydrogen Evolution from Neutral Water Under Aerobic Conditions Catalyzed by Cobalt-microperoxidase-11,"  J. Am. Chem. Soc.  20141364-7. http://dx.doi.org/10.1021/ja406818h
Kleingardner, J.G., Bowman, S.E.J., Bren, K.L.  "The Influence of Heme Ruffling on Spin Densities in Ferricytochromes c Probed by Heme Core 13C NMR,"  Inorg. Chem.  20135212933-12946. http://dx.doi.org/10.1021/ic401250d
Kaur, R., Bren, K.L.  "Redox State Dependence of Axial Ligand Dynamics in Nitrosomonas europaea Cytochrome c552,"  J. Phys. Chem. B  201311715720-15728. http://dx.doi.org/10.1021/jp4064577
Lee, A.J., Asher, W.B., Stern, H.A., Bren, K.L., Krauss, T.D.  "Single-molecule Analysis of Cytochrome c Folding by Monitoring the Lifetime of an Attached Fluorescent Probe,"  J. Phys. Chem. Lett.  201342727-2733. http://dx.doi.org/10.1021/jz401259y
Asher, W.B., Bren, K.L.  "Affinity Purification of heme-tagged proteins,"  Methods in Molecular Biology  2013in press.
Can, M., Krucinska, J., Zoppallero, G., Andersen, N.H., Wedekind, J.E., Hersleth, H.P., Andersson, K.K., Bren, K.L.  "Structural Characterization of Nitrosomonas europaea Cytochrome c552 Variants with Marked Differences in Electronic Structure,"  ChemBioChem  2013in press.
Josephs, T.M., Liptak, M.D., Hughes, G., Lo, A., Smith, R.M., Wilbanks, S.M., Bren, K. L., Ledgerwood, E.C.  "Conformational Change and Human Cytochrome c Function: Mutation of Residue 41 Modulates Caspase Activation and Destabilizes Met-80 Coordination,"  J. Biol. Inorg. Chem.  201318289-297.
Bren, K. L.  "NMR Spectroscopy of Paramagnetic Heme Proteins,"  Current Inorganic Chemistry  20122273-291.
Asher, W.B., Bren, K. L.  "Cytochrome c Heme Lyase Can Mature a Fusion Peptide Composed of the Amino-terminal Residues of Horse Cytochrome c,"  Chem Comm.  2012488344-8346.
Galinato, M.G.I., Kleingardner, J.G., Bowman, S.E.J., Alp, E.E., Zhao, J., Bren, K. L., Lehnert, N.  "Heme-Protein Vibrational Couplings in Cytochrome c Provide a Dynamic Link that Connects the Heme-Iron and the Protein Surface,"  Proc. Natl. Acad. Sci. USA  20121098896-8900.
Can, M., Zoppellaro, G., Andersson, K. K., Bren, K. L.  "Modulation of Ligand-Field Parameters by Heme Ruffling in Cytochromes c Revealed by EPR Spectroscopy,"  Inorg. Chem.  20115012018-12024.
Levin, B. D., Can, M., Bowman, S. E. J., Bren, K. L., Elliott, S. J.  "Methionine Ligand Lability in Bacterial Monoheme Cytochromes c: An Electrochemical Study,"  J. Phys. Chem. B.  201111511718-11726.
Kleingardner, J. G., Bren, K. L.  "Comparing substrate specificity between cytochrome c maturation and cytochrome c heme lyase systems for cytochrome c biogenesis,"  Metallomics  20113396-403.
Chung, J. K., Thielges, M. C., Bowman, S. E. J., Bren, K. L., Fayer, M. D.  "Temperature Dependent Equilibrium Native to Unfolded Protein Dynamics and Properties Observed with IR Absorption and 2D IR Vibrational Echo Experiments,"  J. Am. Chem. Soc.  20111336681-6691.
Liptak, M. D., Fagerlund, R. D., Ledgerwood, E. C., Wilbanks, S. M., Bren, K. L.  "The Proapoptotic G41S Mutation to Human Cytochrome c Alters the Heme Electronic Structure and Increases the Electron Self-Exchange Rate,"  J. Am. Chem. Soc.  20111331153-1155.
Lee, A. J., Ensign, A. A., Krauss, T.D., Bren, K. L.  "Zinc Porphyrin as a Donor for FRET in Zinc Cytochrome c,"  J. Am. Chem. Soc.  20101321752-7153.
Liptak, M. D., Wen, X., Bren, K. L.  "NMR and DFT Investigation of Heme Ruffling: Functional Implications for Cytochrome c,"  J. Am. Chem. Soc.  20101329753-9763.
Asher, W. B., Bren, K. L.  "A Heme Fusion Tag for Protein Affinity Purification and Quantitation,"  Protein Science  2010.
Bowman, S. E. J., Bren, K. L.  "Variation and Analysis of Second-sphere Interactions and Axial Histidinate Character in c-type Cytochromes,"  Inorg. Chem.  201049.
Zoppellaro, G., Bren, K. L., Ensign, A. A., Harbitz, E., Kaur, R., Hersleth, H.-P., Ryde, U., Hederstedt, L., Andersson, K. K.  "Review: Studies of ferric heme proteins with highly anisotropic/highly axial low spin (S = 1/2) electron paramagnetic resonance signals with bis-Histidine and histidine-methionine axial iron coordination,"  Biopolymers  2009911064-1082.
Michel, L. V., Bren, K. L.   "Submolecular Unfolding Units of Pseudomonas aeruginosa Cytochrome c551,"  J. Biol. Inorg. Chem.  200813837-845.
Bowman, S. E. J., Bren, K. L.  "The Chemistry and Biochemistry of Heme c: Functional Bases for Covalent Attachment,"  Nat. Prod. Rep.   2008251118-1130.
Zoppellaro, G., Harbitz, E., Kaur, R., Ensign, A. A., Bren, K. L., Andersson, K. K.  "Modulation of the Ligand-field Anisotropy in a Series of Ferric Low Spin Cytochrome c Mutants Derived from Pseudomonas aeruginosa Cytochrome c-551 and Nitrosomonas europaea Cytochrome c-552, An EPR and NMR Study,"  J. Am. Chem. Soc.  200813015348-15360.
Michel, L. V., Ye, T., Bowman, S. E. J., Levin, B. D., Hahn, M. A., Russell, B. S., Elliott, S. J., Bren, K. L.  "Heme Attachment Motif Mobility Tunes Cytochrome c Redox Potential,"  Biochemistry   20074611753-11760.
Wen, X., Patel, K. M., Russell, B. S., Bren, K. L.   "Effects of Heme Pocket Structure and Mobility on Cytochrome c Stability,"  Biochemistry   2007462537-2544.
Zhong, L., Wen, X., Rabinowitz, T. M., Russell, B. S., Karan, E. F., Bren, K. L.  "Heme Axial Methionine Fluxionality in Hydrogenobacter thermophilus Cytochrome c552,"  Proc. Natl. Acad. Sci. U.S.A.  20041018637-8642.
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Professor Bren's Contact Information...

Office: Hutchison 448
Phone: (585) 275-4335


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