New Publication By BellBrook Scientists – Methyltransferase Assays
New Publication By BellBrook Scientists – Development and Validation of a Generic Methyltransferase Enzymatic Assay Based on an SAH Riboswitch
A group of BellBrook scientists was recently published in SLAS Discovery for their research, “Development and Validation of a Generic Methyltransferase Enzymatic Assay Based on an SAH Riboswitch.” In this article, scientists demonstrate the development of the assay and validate a variety of methyltransferases, including PRMT4, PRMT5, DOT1L, METTL3/METTL14, and nsp14.
Methylation of histones, DNA, and RNA is a significant epigenetic regulatory process linked to various therapeutic areas, such as metabolic diseases, cardiovascular issues, cancer, inflammation/autoimmunity, and neurodegenerative conditions. For these reasons, discovering methyltransferase inhibitors is a hotly researched area.
Many methyltransferase enzymes have slow turnover rates and low Kms for SAM. A generic and versatile assay for detecting and quantifying methyltransferase enzyme activity was necessary to uncover bonafide inhibitors. Previous assays did not have the sensitivity necessary to accurately study these enzymes in a robust HTS format.
The assay utilizes an S-adenosylhomocysteine (SAH) riboswitch, an RNA element that binds explicitly to SAH, to detect the presence of SAH resulting from methyltransferase activity. This interaction is measured to determine enzyme activity.
This new assay presents a robust and versatile method for studying methyltransferases, which play a crucial role in numerous biological and pathological processes. Its applications in research and drug discovery, particularly for diseases associated with methylation dysregulation, could help lead to novel therapeutics.
