Graduated in 1982 from Texas Tech University.

Enzymology; Biological electron transfer; Protein structure-function relationships; Protein biosynthesis; biosensors.

Fundamental Mechanisms of Enzyme Catalysis, Biological Electron Transfer, Molecular Recognition, Protein Biosynthesis and Posttranslational Modification. My ongoing research program concerns the study of enzyme mechanisms, protein structure-function relationships, protein-protein interactions, protein biosynthesis, and mechanisms of long range biological electron transfer. My research has focused on quinoprotein dehydrogenases. These redox enzymes are relatively distinct for two reasons. They utilize enzyme-bound quinones as prosthetic groups, and for electron acceptors they use other proteins rather than oxygen or pyridine nucleotides. These enzymes are soluble and have been crystallized free and in complex with their physiologic redox partners. This allows us to correlate structural information with the results of our biochemical and biophysical studies. Our mechanistic enzymology studies which include site-directed mutagenesis are allowing us to better understand the molecular mechanisms of cofactor-mediated enzyme-catalyzed reactions. Elucidation of factors which influence specific protein-protein interactions between quinoproteins and their electron acceptors is providing insight into the process of protein-protein recognition which is common to a wide range of biologic phenomena. Description of the mechanism of biosynthesis of quinoproteins and their cofactors is relevant to understanding the mechanisms of biosynthesis of complex redox proteins, as well as mechanisms of protein biosynthesis and posttranslational modification of proteins. Characterization of the mechanisms and pathways of long range intermolecular electron transfer will allow us to better understand the fundamental processes of respiration and photosynthesis at the molecular level.

Protein Engineering. Using the detailed structural and mechanistic information which has been obtained for the proteins under study, site-directed mutagenesis has been used to redesign proteins to specifically alter their function. Some examples of what has been accomplished include the following. The substrate specificity of methylamine dehydrogenase was changed to that of a long chain dehydrogenase. A cation-binding site in that enzyme was altered to change the sensitivity of the enzyme to specific cations. Binding constants for protein-protein interactions have been altered. The redox potential and other parameters that control electron transfer rates have been altered by specific mutations. Thus far, site-directed mutagenesis has primarily been used as a tool to study protein structure-function relationships. With the expertise and insight that has been gained from these studies, future plans will include using this approach as a tool to logically design mutations that will alter enzyme function for specific purposes.

Analytical Applications of Enzymes and Redox Proteins. A detailed understanding of the structure and function of redox enzymes is also providing us with the opportunity to exploit their specificity, and electron transfer properties, for use as components of bioanalytical sensing devices, so called enzyme electrodes or biosensors. An amine dehydrogenase was incorporated into an enzyme electrode that can be used to quantitate histamine levels in solution. Site-directed mutagenesis was also used to re-engineer that enzyme in a manner which improved the detection limit for histamine when it was incorporated into the biosensor. These studies will be continued and expanded to include other enzymes to detect specific compounds of interest. This will be done with an eye towards developing biosensors with potential commercial applications.

Areas of Expertise. My research program utilizes essentially all techniques and approaches of modern biochemistry, biophysics and molecular biology. Expertise in my laboratory includes development of novel systems for heterologous expression of proteins, site-directed mutagenesis, protein purification, steady-state and transient kinetic techniques, protein chemistry, spectroscopy, electrochemical analysis and molecular modeling. Collaborative work includes x-ray crystallography, NMR and EPR spectroscopy.

Davidson, V.L. (2000) What controls rates of interprotein electron transfer reactions. Acc. Chem. Res. 33, 87-93.

Davidson, V.L., Jones, L.H., Graichen, M.E. & Zhu, Z. (2000) Tyr 30 of amicyanin is not critical for electron transfer to cytochrome c-551i: Implications for predicting electron transfer pathways. Biochim. Biophys. Acta 1457, 27-35.

Singh, V., Zhu, Z., Davidson, V.L. & McCracken, J.L. (2000) Characterization of the tryptophan tryptophyl-semiquinone catalytic intermediate of methylamine dehydrogenase by electron spin echo envelope modulation spectroscopy. J. Am. Chem. Soc. 122, 931-938.

Davidson, V.L. (2000) The effects of kinetic coupling on experimentally determined electron transfer parameters. Biochemistry 39, 4924-2928.

Zeng, K., Tachikawa, H., Zhu, Z. & Davidson, V.L. (2000) Amperometric detection of histamine with a methylamine dehydrogenase polypyrrole based sensor. Anal. Chem. 72, 2211-2215.

Davidson, V.L. (2001) pyrroloquinoline quinone (pqq) from methanol dehydrogenase and tryptophan tryptophylquinone (ttq) from methylamine dehydrogenase. Adv. Protein Chem. 58, 95-140.

Zhu, Z., Graichen, M.E., Jones, L.H. & Davidson, V.L. (2000) Molecular basis for complex formation between methylamine dehydrogenase and amicyanin revealed by inverse mutagenesis of an interprotein salt bridge. Biochemistry 39, 8830-8836.

Zhu, Z., Sun, D. & Davidson, V.L. (2000) conversion of methylamine dehydrogenase to a long-chain amine dehydrogenase by mutagenesis of a single residue. Biochemistry 39, 11184-11186.

Sun, D., Jones, L.H., Mathews, F.S., & Davidson, V.L. (2001) active site residues are critical to the folding and stability of methylamine dehydrogenase. Protein Eng. 14, 675-681.

Davidson, V.L. & Sun, D. (2002) Lysozyme-osmotic shock methods for the localization of periplasmic redox proteins in bacteria. Methods Enzymol. 353, 121-130.

Sun, D. & Davidson, V.L. (2001) re-engineering monovalent cation binding sites of methylamine dehydrogenase: effects on spectral properties and gated electron transfer. Biochemistry 40, 12285-12291.

Bao, L., Sun, D., Tachikawa, H., & Davidson, V.L. (2002) Improved sensitivity of a histamine sensor using an engineered methylamine dehydrogenase. Anal. Chem. 74, 1144-1148.

Wang, Y., Sun, D. & Davidson, V.L. (2002) Use of indirect site-directed mutagenesis to alter the substrate specificity of methylamine dehydrogenase. J. Biol. Chem. 277, 4119-4122.

Sun, D. & Davidson, V.L. (2002) Inter-subunit cross-linking of methylamine dehydrogenase by cyclopropylamine requires residue aPhe55. FEBS Lett. 517, 172-174.

Sun, D., Wang, X., & Davidson, V.L. (2002) Redox properties of an engineered purple CuA azurin. Arch. Biochem. Biophys. 404, 158-162.

Sun, D. & Davidson, V.L. (2002) Mechanisms of catalysis and electron transfer by tryptophan tryptophylquinone enzymes. Prog. React. Kinet. 27, 209-241.

Sun, D., Chen, Z-W., Mathews, F.S. & Davidson, V.L. (2002) Mutation of αPhe55 of methylamine dehydrogenase alters the reorganization energy and electronic coupling for its electron transfer reaction with amicyanin. Biochemistry 41, 13926-13933.

Davidson, V.L. (2002) Chemically gated electron transfer. A means of accelerating and regulating rates of biological electron transfer. Biochemistry 41, 14633-14636.

Sun, D. & Davidson, V.L. (2003) Effects of engineering uphill electron transfer into the methylamine dehydrogenase-amicyanin-cytochrome c-551i complex. Biochemistry 42, 1772-1776.

Davidson, V.L. (2003) Probing mechanisms of catalysis and electron transfer by ethylamine dehydrogenase by site-directed mutagenesis of aphe55. Biochim. Biophys. Acta 1647, 230-233.

Davidson, V.L. & Sun, D. (2003) Evidence for substrate activation of electron transfer from methylamine dehydrogenase to amicyanin. J. Am. Chem. Soc.125, 3224-3225.

Pearson, A.R., Jones, L.H., Higgins, L., Ashcroft, A.E., Wilmot, C.M., & Davidson, V.L. (2003) Understanding quinone cofactor biogenesis in methylamine dehydrogenase through novel cofactor generation. Biochemistry 42, 3224-3230.

Wang, Y., Graichen, M.E., Liu, A., Pearson, A.R., Wilmot, C.M., & Davidson, V.L. (2003) MauG, a novel diheme protein required for tryptophan tryptophylquinone biogenesis. Biochemistry, 42, 7318-7325.

Sun, D., Ono, K., Okajima, T., Tanizawa, K., Uchida, M., Yamamoto, Y., Mathews, F.S. & Davidson, V.L. (2003) Chemical and kinetic reaction mechanisms of quinohemoprotein amine dehydrogenase from Paracoccus denitrificans. Biochemistry 42, 10896-10903.

Xia, Z-X., Dai, W-W., He, Y-N., White, S.A., Mathews, F.S., & Davidson, V.L. (2003) X-ray structure of methanol dehydrogenase from Paracoccus denitrificans and molecular modeling of its interactions with cytochrome c-551i. J. Biol. Inorg. Chem. 8, 843-854.

Jones, L.H., Liu, A., & Davidson, V.L. (2003) An engineered Cua amicyanin capable of intermolecular electron transfer reactions. J. Biol. Chem. 278, 47269-47274.

Ferrari, D., Di Valentin, M., Carbonera, D., Merli, A., Chen, Z-w., Mathews, F.S., Davidson, V.L. & Rossi, G-L. (2004) Electron transfer in crystals of the binary and ternary complexes of MADH with amicyanin and cytochrome c551i as detected by EPR spectroscopy. J. Biol. Inorg. Chem. 9, 231-237.

Pearson, A.R., de la Mora-Rey, T., Graichen, M.E., Wang, Y., Jones, L.H., Marimanikkupam, S.,  Aggar, S.A., Grimsrud, P.A., Davidson, V.L., & Wilmot, C.M. (2004) Further insights into quinone cofactor biogenesis: Probing the role of mauG in methylamine dehydrogenase TTQ formation. Biochemistry 43, 5494-5502.

Carrell, C.J., Sun, D., Jiang, S, Davidson, V.L. & Mathews, F.S. (2004) Structural studies of two mutants of amicyanin from Paracoccus denitrificans that stabilize the reduced state of the copper. Biochemistry 43, 9372-9380.

Carrell, C.J., Wang, X., Jones, L.H., Jarrett, W.L., Davidson, V.L. & Mathews, F.S. (2004) Crystallographic and NMR investigation of cobalt-substituted amicyanin. Biochemistry 43, 9381-9389.

Davidson, V.L. (2004) Electron transfer in quinoproteins. Arch. Biochem. Biophys. 428, 32-40.

Sukumar, N., Langan, P., Mathews, F.S., Jones, L.H., Thiyagarajan, P., Schoenborn, B.P. & Davidson, V.L. (2005) A preliminary time-of-flight neutron diffraction study on amicyanin from Paracoccus denitrificans. Acta Cryst. D61, 640-642.

Jones, L.H., Pearson, A.R., Tang, Y., Wilmot, C.M., & Davidson, V.L. (2005) Active site aspartate residues are critical for tryptophan tryptophylquinone biogenesis in methylamine dehydrogenase. J. Biol. Chem. 280, 17392-17396.

Davidson, V.L. (2005) Structure and mechanism of tryptophylquinone enzymes. Bioorg. Chem., in press.

Sun, D., Li, X., Mathews, F.S. & Davidson, V.L. (2005) Site-directed mutagenesis of proline 94 to alanine in amicyanin converts a true electron transfer reaction into one that is kinetically coupled. Biochemistry, in press.