Protein Arginine
Methylation

Moonlighting
Proteins

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At the heart of all protein functions, whether they are enzymatic or structural, is protein structure. In turn, the function of individual proteins can be altered by small molecules, covalent modifications, and protein-protein interactions. This makes ascribing function to the vast proteome very daunting. Since protein-protein and protein-DNA interactions are vital for a multitude of mammalian cellular processes, understanding the determinants for binding, the potential structural and functional changes in each protein, and the function of the resultant complex is fundamental to not only understanding basal cellular communication but also what happens when the cellular environment deviates as in a disease state, stress, or cancer. Our group is interested in studying how protein structure is utilized by a cell to communicate a particular response.  We employ molecular biology techniques, site-directed mutagenesis, enzyme kinetics, protein structure methodologies, protein-protein interaction probes, and transient transfections. Our group studies two systems (Moonlighting Proteins & Protein Arginine Methylation) to gain a better understanding of how protein structures govern function.

Publications:

Wooderchak, W.L, Zhang, T., Zhou, Z.S., Acuna, M. Tahara, S., & Hevel*, J.M. (2008) PRMT1 Dissociatively Methylates Sequence Motifs that Go Beyond the ‘RGG’ and ‘RXR’ Paradigm.” to Biochemistry, in press.

Hevel*, J.M., Pande, P., Oveson, S., Sudweeks, T. Hansen, C. & Ayling, J.E. (2008) Determinants of Oligomerization of the Bifunctional Protein DCoHalpha and the Effect on its Coactivator and Enzymatic Activities. Archives Biochemistry and Biophysics, in press.

Hevel*, J.M., Olson-Buelow, L., Ganesa, B., Stevens, J.R., Hardman, J.P., & Aust, A.E. (2008) Novel Functional View of the Crocidolite-Treated A549 Human Lung Epithelial Transcriptome Reveals an Intricate Network of Pathways with Opposing Functions. BMC Genomics, in press.

Dorgan, K.M., Wooderchak, W.L., Wynn, D.P., Karschner,E.L., Alfaro, J.F., Cuig, Y., Zhou, Z.S., and Hevel, J.M. (2006) An Enzyme-Coupled Continuous Spectrophotometric Assay for S- Adenosylmethionine-Dependent Methyltransferases. Analytical Biochemistry, 350:249-255.

Hevel, J.M.*, Stewart, J.A., Gross, K.L., & Ayling, J.E. (2006) Can the DCoHalpha Isozyme Compensate in Patients with 4a-Hydroxy-tetrahydrobiopterin Dehydratase/DCoH Deficiency? Molecular Genetics and Metabolism 88:38-46.

Hoffmann, D., Hevel, J.M., Moore, R.E. & Moore, B.S. (2003) Sequence analysis and biochemical characterization of the nostopeptolide A biosynthetic gene cluster from Nostoc sp. GSV224. Gene 311:171-80.

Luesch, H., Hoffmann, D., Hevel, J.M., Becker, J., Golakoti, T. & Moore, R.E. (2003) Biosynthesis of 4-methylproline in cyanobacteria: Cloning of nosE and nosF genes and biochemical characterization of encoded dehydrogenase and reductase activities. J Org Chem 68:83-91.

Hevel, J.M., Mills, S.A., & Klinman, J.P. (1999) Mutation of a strictly conserved, active-site residue alters substrate specificity and cofactor biogenesis in a copper amine oxidase. Biochemistry 38(12): 3683-93.

White, K.A., Pufahl, R.A., Olken, N.M., Hevel, J.M., Richards, M.R. and Marletta, M.A. (1994). Nitric oxide synthase: mechanism and relationship to cytochrome P-450. In: Cytochrome P-450: Biochemistry, Biophysics and Molecular Biology John Libbey Eurotext Limited, France, pp.43-48.

Hevel, J.M. & Marletta, M.A. (1994). Nitric oxide synthase assays. In: Methods in Enzymology 233:250-258.

Hevel, J.M. and Marletta, M.A. (1993) Macrophage nitric oxide synthase: tetrahydrobiopterin decreases the NADPH stoichiometry. Advances in Experimental Medicine and Biology 338:285-8.

Hevel, J.M. & Marletta, M.A. (1992) Macrophage nitric oxide synthase: relationship between enzyme-bound tetrahydrobiopterin and synthase activity. Biochemistry 31:7160-7165.

Mulligan, M.S., Hevel, J.M., Marletta, M.A., & Ward, P.A. (1991) Tissue injury caused by deposition of immune complexes is L-arginine dependent. Proc. Natl. Acad. Sci. USA 88:6338-6342.

Hevel, J.M., White, K.A., & Marletta, M.A. (1991) Purification of the inducible murine macrophage nitric oxide synthase. J. Biol. Chem. 266:22789-22791.

Hevel, J.M., White, K.A., & Marletta, M.A. (1991) Purification of the inducible murine macrophage nitric oxide synthase: identification as a flavoprotein and detection of enzyme-bound tetrahydrobiopterin. In: Biology of Nitric Oxide: Physiology, Pathophysiology, Pharmacology and Clinical Significance (S. Moncada, M.A. Marletta and J.B. Hibbs, Jr., eds.) pp. 19-21.

Marletta, M.A.,Tayeh, M., & Hevel, J.M. (1990) Unraveling the biological significance of nitric oxide. BioFactors 2:219-25.