Our research employs a broad range of biochemical, biophysical and molecular biology approaches to elucidate enzyme mechanisms, protein structure-function relationships, mechanisms of posttranslational modification of proteins, and biological energy metabolism.A general goal of this research is to describe how specific enzymes control the transfer of reactive electrons and the activation of molecular oxygen, while minimizing oxidative damage. The ability to do this is central to cell development, health and survival. Reactive oxygen species and free radicals are produced as by-products of biological electron transfer and oxygen metabolism. Defining the mechanisms of long range electron transfer reactions will enhance our understanding of the fundamental processes of respiration and intermediary metabolism at the molecular level. An understanding of the mechanisms of control of biological electron transfer reactions will provide insight into how defective protein electron transfer leads to production of free radicals and reactive oxygen species which cause non-specific oxidative damage to cell components that is associated with mitochondrial myopathies, oxidative stress, many disease states, and aging.Free radicals and reactive oxygen species are also required for, and used productively in biosynthetic processes. An example of such a process is the biosynthesis of protein-derived cofactors. Recent advances in enzymology, structural biology and protein chemistry have documented that catalytic and redox-active prosthetic groups may be derived from posttranslational modification of amino acid residues of proteins. These protein-derived cofactors typically arise from oxygenation of aromatic residues, covalent cross-linking of amino acid residues, or cyclization or cleavage of internal amino acid residues. Studies of the biosynthesis and function of protein-derived cofactors are revealing novel chemical mechanisms for both the biosynthesis of the cofactors and the reactions that they subsequently catalyze. The characterizations of protein-derived cofactors and their mechanisms of biosynthesis introduces a new dimension to our current views about protein evolution and protein structure-function relationships, and provides insight for protein engineering strategies to introduce new functional groups into proteins.

Selected Recent Publications

  1. Williamson, H.R., Dow, B.A. & Davidson, V.L. (2014) Mechanisms for control of biological electron transfer reactions Bioorganic Chemistry 57, 213-221.
  2. Shin, S., Choi, M., Williamson, H.R. & Davidson, V.L. (2014) A simple method to engineer a protein-derived redox cofactor for catalysis. Biochimica Biophysica Acta BBA-Bioenergetics, 1837, 1595-1601.
  3. Davidson, V.L. (2014) Protein-derived Cofactors. In: Encyclopedia of Life Sciences. John Wiley & Sons, Ltd: Chichester. [DOI:10.1002/9780470015902.a0000664.pub3].
  4. Dow, B.A., Sukumar, N., Matos, J.O., Choi, M., Schulte, A., Tatulian, S.A. and Davidson, V.L. (2014) The sole tryptophan of amicyanin enhances its thermal stability but does not influence the electronic properties of the type 1 copper site. Arch. Biochem. Biophys. 550, 20-27.
  5. Shin, S., Yukl, E.T., Sehanobish, E., Wilmot, C.M. & Davidson, V.L. (2014) Site-directed mutagenesis of Gln103 reveals the influence of this residue on the redox properties and stability of MauG. Biochemistry 53, 1342-1349.
  6. Sehanobish, E., Shin, S., Sanchez-Amat, A. & Davidson, V.L. (2014) Steady-state kinetic mechanism of LodA, a novel cysteine tryptophylquinone-dependent oxidase. FEBS Lett. 588, 752-756.
  7. Shin, S. & Davidson, V.L. (2014) MauG, a diheme enzyme that catalyzes tryptophan tryptophylquinone biosynthesis by remote catalysis. Arch. Biochem. Biophys. 544, 112-118.
  8. Davidson, V.L. & Wilmot, C.M. (2013) Post-translational biosynthesis of the protein-derived cofactor tryptophan tryptophylquinone. Annu. Rev. Biochem. 82, 531-550.
  9. Abu Tarboush, N., Yukl, E.T., Shin, S., Feng, M., Wilmot, C.M. & Davidson, V.L. (2013) The carboxyl group of Glu113 is required for stabilization of the diferrous and bis-FeIV states of MauG. Biochemistry 52, 6358-6367.
  10. Geng, J., Dornevil, K., Davidson, V.L. & Liu, A. (2013) Tryptophan-mediated charge resonance stabilization in the bis-Fe(IV) redox state of MauG. Proc. Natl. Acad. Sci. U.S.A. 110, 9639-9644.
  11. Yukl, E.T., Liu, F., Krzystekc, J., Shin, S., Jensen, L.M.R., Davidson, V.L., Wilmot, C.M. & Liu, A. (2013) A di-radical intermediate within the context of tryptophan tryptophylquinone biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 110, 4569-4573.
  12. Abu Tarboush, N., Shin, S., Geng, J., Liu, A. & Davidson, V.L. (2012) Effects of the loss of the axial tyrosine ligand of the low-spin heme of MauG on its physical properties and reactivity. FEBS Lett. 586, 4339-4343.
  13. Choi, M., Shin, S. & Davidson, VL (2012) Characterization of electron tunneling and hole hopping reactions between different forms of MauG and methylamine dehydrogenase within a natural protein complex. Biochemistry 51, 6942-6949.
  14. Feng, M., Jensen, L.M.R., Yukl, E., Wei, X., Liu, A., Wilmot, C.M. & Davidson, V.L. (2012) Proline 107 is a major determinant in maintaining the structure of the distal pocket and reactivity of the high-spin heme of MauG. Biochemistry 51, 1598-1606.
  15. Abu Tarboush, N., Jensen, L.M.R., Yukl, E., Geng, J., Liu, A., Wilmot, C.M. & Davidson, V.L. (2011) Mutagenesis of tryptophan199 suggests that hopping is required for MauG-dependent tryptophan tryptophylquinone biosynthesis. Proc. Natl. Acad. Sci. U.S.A., 108, 16956-16961.
  16. Choi, M. & Davidson, V.L. (2011) Cupredoxins – A study of how proteins may evolve to use metals for bioenergetic purposes. Metallomics, 3, 140-151.
  17. Davidson, V.L. (2011) Generation of protein-derived redox cofactors by posttranslational modification. Mol. BioSyst. 7, 29-37.
  18. Abu Tarboush, N., Jensen, L.M.R., Feng, M., Tachikawa, H., Wilmot, C.M. & Davidson, V.L. (2010) Functional importance of Tyrosine294 and the catalytic selectivity for the bis-Fe(IV) state of MauG revealed by replacement of this axial heme ligand with Histidine. Biochemistry 49, 9783-9791.
  19. Shin, S., Abu Tarboush, N. & Davidson, V.L. (2010) Long range electron transfer reactions between hemes of MauG and different forms of tryptophan tryptophylquinone of methylamine dehydrogenase. Biochemistry 49, 5810-5816.
  20. Sukumar, N., Mathews, F.S., Langan, P. & Davidson, V.L. (2010) A joint x-ray and neutron study on amicyanin revealsthe role of protein dynamics in electron transfer. Proc. Natl. Acad. Sci. U.S.A. 107, 6817-6822.
  21. Jensen, L.M.R., Sanishvili, R., Davidson, V.L. & Wilmot, C.M. (2010) In crystallo posttranslational modification within a MauG/pre-methylamine dehydrogenase complex. Science 327, 1392-1394.
  22. Wilmot, C.M. & Davidson, V.L. (2009) Uncovering novel biochemistry in the mechanism of tryptophan tryptophylquinone cofactor biosynthesis. Curr. Opin. Chem. Biol. 13, 462-467.
  23. Li, X., Fu, R., Lee, S., Krebs, C., Davidson, V.L. & Liu, A. (2008) A catalytic di-heme bis-Fe(IV) intermediate, alternative to an Fe(IV)=O porphyrin radical. Proc. Natl. Acad. Sci. U.S.A. 105, 8597-8600.
  24. Davidson, V.L. (2008) Protein control of true, gated and coupled electron transfer reactions. Acc. Chem. Res. 41, 730-738.

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