Chemistry Faculty: Bryan Knuckley, Ph.D.

Faculty Bio

Associate Professor of Chemistry Office: Science & Engineering (Building 50), Room 3420 Phone: (904) 620-1918 Email:bryan.knuckley@unf.edu Areas of Expertise Dr. Knuckley teaches General Chemistry I Lecture and Laboratory, and Biochemistry. Education Bachelor of Science - University of South Carolina 2003 Ph.D. - University of South Carolina 2009 Postdoctoral Research - The Scripps Research Institute 2010-2012

Research

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.

Funding

• UNF College of Arts and Sciences Deans Leadership Fellowship Grant ($4,000), 2017
• UNF Academic Technology Grant ($2,150), 2017
• University of North Florida, Scholars Transforming Academic Research, 2015
• University of North Florida, Faculty Development Scholarship Grant, 2015
• University of North Florida, College of Arts and Sciences Deans Leadership Fellowship Grant, 2013
• University of North Florida, Faculty Development Scholarship Grant, 2013

Recent Publications

"Histone H4-based peptoids are inhibitors of Protein Arginine Methyltransferase 1 (PRMT1)”, Mann, S.A., DeMart, M.K., May, B., Causey, C.P., Knuckley, B.*, Biochemical Journal, (2020). https://doi.org/10.1042/BCJ20200534
"The development and characterization of a chemical probe targeting PRMT1 over PRMT5,” Mann, S.A., Salsburg, A., Causey, C.P., Knuckley, B.*, Bioorganic & Medicinal Chemistry, 27, 224 – 229, (2019). https://doi.org/10.1016/j.bmc.2018.12.001
"Mechanistic Studies on the Agmatine Deiminase from Listeria monocytogenes," Soares, C. A. and Knuckley, B.*, Biochemical Journal, 473, 1553 - 1561 (2016). http://dx.doi.org/10.1042/BCJ20160221
"Development of a Plate-Based Screening Assay to Investigate the Substrate Specificity of the PRMT Family of Enzymes," Nguyen, H. C., Wang, M., Salsburg, A., Knuckley, B.*, ACS Combinatorial Science, 17, 500-505 (2015). http://dx.doi.org/10.1021/acscombsci.5b00070
"Development of a clickable activity-based protein profiling (ABPP) probe for agmatine deiminases," Marchenko, M., Thomson, A., Ellis, Terri N., Knuckley, B.*, and Causey, C.P*,. Bioorganic and Medicinal Chemistry, (23)9, 2159-2167 (2015). http://dx.doi.org/10.1016/j.bmc.2015.03.013
"Design, synthesis, and in vitro evaluation of an activity-based protein profiling (ABPP) probe targeting agmatine deiminases," Thomson, A., O'Connor, S., Knuckley, B., and Causey, C.P*, Bioorganic and Medicinal Chemistry, 22(17), 4602-4608, (2014). http://dx.doi.org/10.1016/j.bmc.2014.07.028
"Mechanistic studies of Protein Arginine Deiminase 2: Evidence for a substrate-assisted mechanism," Dreyton, C.J., Knuckley, B., Jones, J.E., Lewallen, D.M., Thompson, P.R*, Biochemistry, 53, 4426-4433, (2014). http://dx.doi.org/10.1021/bi500554b