Joan M. HevelJoan M. Hevel

R. Gaurth Hansen Assistant Professor
Biochemistry
B.S., 1988, Lebanon Valley College
Ph.D., 1993, University of Michigan
Postdoctoral, 1993-1996, University of California, Berkeley
Postdoctoral, 1997-1999, University of Hawaii, Manoa
Postdoctoral & Instructor, 2000-2003, University of South Alabama
435.797.1622 jhevel@cc.usu.edu
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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 even more 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. Summarized below are two systems we are using to gain a better understanding of how protein structures govern function.

The Bi-Functional Proteins DCoH and DCoHα
DCoH and DCoHα are mammalian bi-functional proteins that act both as enzymes to dehydrate 4a-hydroxy-tetrahydrobiopterin and as coactivators of transcription by complexing with the transcription factor HNF1α. Mutations in these proteins have been associated with hyperphenylalaninemia and diabetes, respectively. HNF1αhas further been implicated in development and carcinogenesis. Our goals are to 1) understand how the two functions of DCoH(α) are regulated, 2) determine the molecular mechanism of DCoH(α)-dependent coactivation of HNF1α-dependent transcription, and 3) ascertain how particular residue differences alter the functions of DCoH and DCoHα.

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Protein Arginine Methylation

Post-translational modification of specific arginine residues of particular proteins by the additional of a methyl group is catalyzed by a family of enzymes known as the protein arginine methyl transferases (PRMTs). These PRMTs are similar to the well-studies DNA-methyltransferases in that they both use Sadenosyl methionine (SAM) as the methyl donor. The cellular response to methylation of target arginine residues within various proteins is protein-specific and has been shown to include changes in subcellular location, altered transcription rates, and the modulation of protein-protein interactions. We are interested in 1) identifying the repertoire of proteins that are methylated, 2) ascribing function to the post-translationally modified proteins and 3) understanding how the level and pattern of protein methylation changes as a function of cellular stress or disease state.

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Selected Publications:

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

Dorgan, K.M.; Wooderchak, W.L.; Wynna, D.P.; Karschnere, E.L.; Alfaroa, J.F.; Cuig, Y.; Zhoua, Z.S.; Hevel, J.M., “An Enzyme-Coupled Continuous Spectrophotometric Assay for S-Adenosylmethionine-Dependent Methyltransferases,” Analytical Biochemistry, 2006, 350, 249-255.

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

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