|Name||Ms. Sarah Mann|
|Organization or Institution||University of North Florida|
|Topic||Biochemistry / Chem Bio.|
Investigating the variation in substrate specificity between type I and type II PRMT isozymes
Sarah Mann, Bryan Knuckley
University of North Florida
Protein arginine methyltransferases (PRMTs) are a group of mammalian enzymes that modify histone tails by methylating arginine residues. There are nine enzymes in the PRMT family (PRMT1-9), each varying in substrate specificity. PRMT1, which catalyzes the formation of asymmetric dimethylarginine (ADMA), leads to the activation of tumor suppressor genes. By contrast, PRMT5 catalyzes the formation of symmetric dimethylarginine (SDMA), leading to the repression of tumor suppressor genes. Overexpression of PRMTs is associated with the onset of various cancers (i.e. breast cancer and prostate cancer), making PRMTs possible drug targets. To study the differences in substrate specificity of the enzymes, a peptide library was synthesized in a 96-well plate and screened against both PRMT1 and PRMT5 using a high-throughput screening methodology developed in our lab. The screens resulted in the identification of seven potential substrates for PRMT 1 and five potential substrates for PRMT5. The substrates are currently being synthesized and will be further analyzed using a radioactive assay to validate they are true substrates of the enzyme. Comparing the differences in substrate specificity between PRMT1 and PRMT5 will aid in the synthesis of PRMT-specific inhibitors.