2. Academic Validation
  3. Chemical probes for protein arginine methyltransferases

Chemical probes for protein arginine methyltransferases

  • Methods. 2020 Mar 15:175:30-43. doi: 10.1016/j.ymeth.2019.11.017.
Alice Shi Ming Li 1,  Fengling Li 2,  Mohammad S Eram 2,  Albina Bolotokova 2,  Carlo C Dela Seña 2,  Masoud Vedadi 3
Affiliations

Affiliations

  • 1 Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • 2 Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • 3 Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: m.vedadi@utoronto.ca.
PMID: 31809836 DOI: 10.1016/j.ymeth.2019.11.017
Abstract

Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups to specific arginine residues of their substrates using S-adenosylmethionine as a methyl donor, contributing to regulation of many biological processes including transcription, and DNA damage repair. Dysregulation of PRMT expression is often associated with various diseases including cancers. Different methods have been used to characterize the activities of PRMTs and determine their kinetic parameters including mass spectrometry, radiometric, and antibody-based assays. Here, we present kinetic characterization of PRMTs using a radioactivity-based assay for better comparison along with previously reported values. We also report on full characterization of PRMT9 activity with SAP145 peptide as substrate. We further review the potent, selective and cell-active PRMT inhibitors discovered in recent years to provide a better understanding of available tools to investigate the roles these proteins play in health and disease.

Keywords

Arginine methylation; Cancer; Chemical probe; PRMT.

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