Evaluation of kinetic data: What the numbers tell us about PRMTs |
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| Institution: | 1. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA;2. Department of Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA;1. Cell Therapy Center, The University of Jordan, Amman, Jordan;2. Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan;3. Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman, Jordan;4. General Surgery Department/Plastic & Reconstructive, Jordan University Hospital, The University of Jordan, Amman, Jordan;5. Hemostasis and Thrombosis Laboratory, School of Medicine, the University of Jordan, Amman, Jordan;6. Department of Hematology and Oncology, Jordan University Hospital, Amman, Jordan;1. Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, Canada;2. Department of Oncology and Pathology, Karolinska Institutet, Tomtebodavagen 23A, Stockholm, Sweden;1. Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;2. Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA |
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| Abstract: | Protein arginine N-methyltransferase (PRMT) kinetic parameters have been catalogued over the past fifteen years for eight of the nine mammalian enzyme family members. Like the majority of methyltransferases, these enzymes employ the highly ubiquitous cofactor S-adenosyl-l-methionine as a co-substrate to methylate arginine residues in peptidic substrates with an approximately 4-μM median KM. The median values for PRMT turnover number (kcat) and catalytic efficiency (kcat/KM) are 0.0051 s?1 and 708 M?1 s?1, respectively. When comparing PRMT metrics to entries found in the BRENDA database, we find that while PRMTs exhibit high substrate affinity relative to other enzyme-substrate pairs, PRMTs display largely lower kcat and kcat/KM values. We observe that kinetic parameters for PRMTs and arginine demethylase activity from dual-functioning lysine demethylases are statistically similar, paralleling what the broader enzyme families in which they belong reveal, and adding to the evidence in support of arginine methylation reversibility. |
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