个人简介

Ph.D. 1996, California Institute of Technology

研究领域

Bioinorganic and biophysical chemistry

Professor Bren's research interests lie in the fields of bioinorganic and biophysical chemistry. The Bren group has developed new methods for engineering and characterizing metalloproteins in the cytochrome c family, contributing to our understanding of how protein structure dictates protein dynamics and function. In ongoing work, we are employing a range of spectroscopic techniques to understand how the three-dimensional structure of metalloproteins influences their electronic structure and reactivity. In another major effort, the Bren group is developing metalloprotein- and metallopeptide-based catalysts with particular relevance to energy conversion. Metallobiomolecular catalysts offer a number of advantages including being water soluble and environmentally friendly. Furthermore, the use of protein engineering facilitates the preparation of multifunctional and modular structures and the manipulation of second-sphere interactions within the catalytic site. A current emphasis in the lab is the development of artificial hydrogenases, or enzymes that catalyze the reduction of protons derived from water to hydrogen (H2). Hydrogen produced from water is a green, carbon-free fuel, and hydrogen evolution driven by sunlight stores solar energy in the form of chemical bonds. The Bren group's artificial hydrogenases couple to synthetic, biomolecular, or nanotechnological photosensitizers to yield environmentally friendly assemblies to produce hydrogen as a solar fuel. The ultimate goal is to produce elegant and efficient systems that perform artificial photosynthesis.

近期论文

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Asher, W.B., Bren, K.L. "Affinity Purification of Heme-tagged Proteins," Protein Affinity Tags: Methods and Protocols, Springer (New York) 2014, vol. 1177, 17-33. 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 2014, 111, 6570-6575. 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. 2014, 136, 4-7. 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. 2013, 52, 12933-12946. 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 2013, 117, 15720-15728. 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. 2013, 4, 2727-2733. http://dx.doi.org/10.1021/jz401259y Asher, W.B., Bren, K.L. "Affinity Purification of heme-tagged proteins," Methods in Molecular Biology 2013, in 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 2013, in 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. 2013, 18, 289-297. Bren, K. L. "NMR Spectroscopy of Paramagnetic Heme Proteins," Current Inorganic Chemistry 2012, 2, 273-291. 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. 2012, 48, 8344-8346. 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 2012, 109, 8896-8900. 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. 2011, 50, 12018-12024. 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. 2011, 115, 11718-11726. Kleingardner, J. G., Bren, K. L. "Comparing substrate specificity between cytochrome c maturation and cytochrome c heme lyase systems for cytochrome c biogenesis," Metallomics 2011, 3, 396-403. 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. 2011, 133, 6681-6691. 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. 2011, 133, 1153-1155. 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. 2010, 132, 1752-7153. Liptak, M. D., Wen, X., Bren, K. L. "NMR and DFT Investigation of Heme Ruffling: Functional Implications for Cytochrome c," J. Am. Chem. Soc. 2010, 132, 9753-9763. 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. 2010, 49. 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 2009, 91, 1064-1082. Michel, L. V., Bren, K. L. "Submolecular Unfolding Units of Pseudomonas aeruginosa Cytochrome c551," J. Biol. Inorg. Chem. 2008, 13, 837-845. Bowman, S. E. J., Bren, K. L. "The Chemistry and Biochemistry of Heme c: Functional Bases for Covalent Attachment," Nat. Prod. Rep. 2008, 25, 1118-1130. 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. 2008, 130, 15348-15360. 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 2007, 46, 11753-11760. Wen, X., Patel, K. M., Russell, B. S., Bren, K. L. "Effects of Heme Pocket Structure and Mobility on Cytochrome c Stability," Biochemistry 2007, 46, 2537-2544. 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. 2004, 101, 8637-8642.