Bryan A. Knuckley

Dr. Knuckley is interested in understanding the substrate specificity, physiological, and pathological roles of a family of proteins called the Protein Arginine Methyltransferases (PRMTs). These nine mammalian enzymes (PRMT 1-9) catalyze the addition of methyl groups on arginine residues within proteins. Dysregulated arginine methylation of proteins has a significant role in the onset and progression of numerous human diseases (i.e., cardiovascular disease, prostate cancer, breast cancer, etc.), which has contributed to these proteins becoming an important therapeutic target. The Knuckley Lab is interested in developing novel methods to characterize the differences in substrate specificity within this family in a high-throughput fashion. Identification of key factors that contribute to the substrate specificity will allow for the development of novel therapeutics.

Dr. Knuckley is also interested in studying the catalytic mechanism of the guanidinium-modifying enzymes (GME) superfamily. A specific member of the GME family, the agmatine deiminase (AgD) is expressed in many pathogenic bacteria. Agmatine deiminase is responsible for converting agmatine to N-carbamoylputrescine with concurrent release of ammonia. This enzyme is believed to play a role in the acid resistance of these bacteria and enhance the innate immune response.