Protein Arginine
Methylation

Moonlighting Proteins

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 S-adenosyl methionine (AdoMet or 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. In this project we employ enzyme kinetics, site-directed mutagenesis, mammalian cell culture, cellular biochemistry techniques such as Westerns and immunoprecipitaitons, crystallography, and mass spectroscopy.

Dorgan, KM, Wooderchak, WL, Wynn, DP, Karschner, EL, Alfaro, JF, Cuig, Y, Zhou, ZS, & Hevel, JM. (2006) An Enzyme-Coupled Continuous Spectrophotometric Assay for S-Adenosylmethionine-Dependent Methyltransferases. Analytical Biochemistry, 350:249-255.

Wooderchak, WL, Zang, T, Zhou, ZS, Acuna, M, Tahara, SM, & Hevel, JM. (2008) Substrate Profiling of PRMT1 Reveals Amino Acid Sequences that Extend Beyond the 'RGG' Paradigm. Biochemistry. in press.