Cecilia Tommos, Ph.D.

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Research Assistant Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics
Graduate Group Affiliations

Contact information
Department of Biochemistry & Biophysics
University of Pennsylvania Perelman School of Medicine
905 Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104-6059
Office: 215-746-2444
Fax: 215-573-7290
Lab: 215-573-7289
Education:
B.S. (Chemistry)
Stockholm University, 1992.
Ph.D. (Biochemistry)
Stockholm University, 1997.
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Description of Research Expertise

We work to delineate the mechanisms by which amino-acid radicals participate in both productive and destructive redox reactions in living organisms. It is becoming increasingly apparent that, in addition to their fundamental role in biochemistry, radical species are intimately involved in the accentuation of numerous disease states. The reactive and highly oxidizing nature of amino-acid radicals presents a significant barrier for experimental characterization. As a result, the fundamental thermodynamic and kinetic properties of these important protein redox molecules remain largely unknown. The a3X model protein family was specifically constructed to study tyrosine and tryptophan radicals. Using a combination of techniques including NMR spectroscopy, protein voltammetry and time-resolved laser spectroscopy we have shown that the a3X proteins: (i) behave structurally as native proteins; (ii) are stable and well-structured across a broad pH range; (iii) contain a unique radical site whose properties, e.g. solvent accessibility, can be altered in a detailed and controlled manner; (iv) can be expressed to site-specifically incorporate unnatural amino acids, providing additional chemical flexibility at the radical site; (v) provide the unprecedented ability to generate reversible tyrosine and tryptophan voltammograms from which formal reduction potentials can be obtained; and (vi) enhance the radical lifetime into the 10s of seconds time scale. The a3X biomimetic system allows us to experimentally address long-standing questions in radical enzymology and oxidative stress.

Selected Publications

M.C. Martínez-Rivera, B.W. Berry, K.G. Valentine, K. Westerlund, S. Hay and C. Tommos: Electrochemical and Structural Properties of a Protein System Designed to Generate Tyrosine Pourbaix Diagrams. J. Am. Chem. Soc. 133: 17786-17795, 2011.

K. Westerlund, S.D. Moran, H.K. Privett, S. Hay, J. Jarvet, B.R. Gibney and C. Tommos: Making a Single-Chain Four-Helix Bundle for Redox Chemistry Studies. Prot. Eng. Des. & Sel. 21: 645-652, 2008.

B.W. Berry, M.M. Elvekrog and C. Tommos: Environmental Modulation of Protein Cation-π Interactions. J. Am. Chem. Soc. 129: 5308–5309, 2007.

S. Hay, K. Westerlund and C. Tommos: Redox Characteristics of a De Novo Quinone Protein. J. Phys. Chem. B 111: 3488–3495, 2007.

K. Westerlund, B.W. Berry, H. Privett and C. Tommos: Exploring Amino-Acid Radical Chemistry: Protein Engineering and De Novo Design. Biochim. Biophys. Acta 1707: 103–116, 2005.

B.R. Gibney and C. Tommos: De Novo Protein Design. Photosystem II - The light-driven water: plastoquinone oxidoreductase. T. Wydrzynski and K. Satoh (eds.). Springer, Dordrecht, 2005.

S. Hay, K. Westerlund and C. Tommos: Moving a Phenol Hydroxyl Group from the Surface to the Interior of a Protein: Effects on the Phenol Potential and pKA. Biochemistry 44: 11891-11902, 2005.

Peterson, R.W., K. Anbalagan, C. Tommos and A.J. Wand: Forced Folding and Structural Analysis of Metastable Proteins. J. Am. Chem. Soc. 126: 9498–9499, 2004.

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Last updated: 10/01/2014
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