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
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
bi-functional proteins that act both as enzymes to
4a-hydroxy-tetrahydrobiopterin and as coactivators of
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
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
methylation of target arginine residues within various
protein-specific and has been shown to include changes in
location, altered transcription rates, and the modulation
protein-protein interactions. We are interested in 1) identifying
repertoire of proteins that are methylated, 2) ascribing function
the post-translationally modified proteins and 3) understanding how
level and pattern of protein methylation changes as a function of
cellular stress or disease state.
Chongyuan Wang, Yuwei Zhu, Tamar B Caceres, Lei Liu, Junhui Peng, Junchen Wang, Jiajing Chen,
Xuwen Chen, Zhiyong Zhang, Xiaobing Zuo, Qingguo Gong, Maikun Teng, Joan M Hevel, Jihui Wu*, and Yunyu Shi* (2014) Structural Determinants for the Strict Monomethylation Activity by Trypanosoma brucei Protein Arginine Methyltransferase 7.
Accepted at Structure
Gui, S, Gathiaka, S, Li, J, Qu, J, Acevedo, O,
& Hevel, JM *
(2014) A remodeled protein arginine
methyltransferase 1 (PRMT1) generates symmetric dimethylarginine. J. Biol. Chem.
January 29, 2014,
Gui, S, Wooderchak-Donahue, WL, Zang, T, Chen, D, Daly, MP, Zhou, ZS, & Hevel*, JM. (2012)
Substrate-Induced Control of Product Formation by Protein Arginine Methyltransferase 1 (PRMT1).
Biochemistry, 52 (1), pp 199–209.
Gui, S., Wooderchak, W.L., Daly, M.P., Porter,
P.J., Johnson, S.J., and Hevel, J.M. (2011)
Investigation of the Molecular Origins of Protein Arginine Methyltransferase I (PRMT1) Product
Specificity Reveals a Role for Two Conserved Methionine Residues J. Biol. Chem. Aug
Hevel, J.M. (2010) Method to Quantify Methyltransferase Activity. Patent application number: 12825548.
Filed on 29 June 2010.
Suh-Lailam, B.B. & Hevel*, J.M. (2010) Rapid, Quantitative Measurement of Protein Methyltransferase Activity. Analytical Biochemistry, 398:Pages 218-224, epub 7 September 2009.
Hevel, J.M. (2009) Method to Quantify Methyltransferase Activity. Provisional patent application number: 61221453. Filed on 29 June 2009.
Suh-Lailam, B.B. & Hevel*, J.M. (2008) Efficient Cleavage of Problematic TEV-PRMT1 Constructs. Analytical Biochemistry, 387:130-2.
Wooderchak, W.L, Zhou, Z.S. & Hevel*, J.M. (2008) Assays for S-Adenosylmethionine (AdoMet/SAM)-Dependent Methyltransferses. Current Protocols in Toxicology, Supplement 38, November 2008, Unit 4.26, Wiley.
Wooderchak, W.L, Zhang, T., Zhou, Z.S., Acuna, M. Tahara, S., & Hevel*, J.M. (2008) Substrate Profiling of PRMT1 Reveals Sequences that Go Beyond the ‘RGG’ Paradigm. Biochemistry, 47:9456–9466, 2008. doi:10.1021/bi800984s
Hevel*, J.M., Pande, P., Oveson, S., Sudweeks, T., , Hansen, C. & Ayling, J.E. (2008) Determinants of Oligomerization of the Bifunctional Protein DCoHa and the Effect on its Coactivator and Enzymatic Activities. Archives of Biochemistry and Biophysics, 477:356-362. doi:10.1016/j.abb.2008.06.023
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, 9:376. doi:10.1186/1471-2164-9-376