Profiling of methyltransferases

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

For this project we developed six unique primary assays for the methyltransferases (MTase) NNMT, PNMT, COMT, HNMT, GNMT, and GAMT. We also developed a counter-assay using the Methyltransferase Glo kit from Promega. To date we have screened 12,000 compounds from Genesis MiniMe, LOPAC, and the Epigenetic Collection to begin building the activity profiles for each MTase. Recently (summer 2020) virtual docking simulations and protein structure comparison efforts were launched to inform hypotheses about compounds which are pan inhibitors of the MTases (e.g., what contacts between compound and amino acid are conserved among these MTases?) and which are selective to individual MTases (e.g., what chemical features are important for inhibiting NNMT vs PNMT or GAMT?). Future plans include screening NPACT (5,000 compounds) and a commercial methyltransferase-targetted library (10,000 compounds) to expand the chemical space explored in this study.