Photoregulation of PRMT-1 Using a Photolabile Non-Canonical Amino Acid

Abstract

Protein methyltransferases are vital to the epigenetic modification of gene expression. Thus, obtaining a better understanding of and control over the regulation of these crucial proteins has significant implications for the study and treatment of numerous diseases. One ideal mechanism of protein regulation is the specific installation of a photolabile-protecting group through the use of photocaged non-canonical amino acids. Consequently, PRMT1 was caged at a key tyrosine residue with a nitrobenzyl-protected Schultz amino acid to modulate protein function. Subsequent irradiation with UV light removes the caging group and restores normal methyltransferase activity, facilitating the spatial and temporal control of PRMT1 activity. Ultimately, this caged PRMT1 affords the ability to better understand the protein’s mechanism of action and potentially regulate the epigenetic impacts of this vital protein.

Cellular and Biophysical Applications of Genetic Code Expansion

“…The introduction of ncAA 30 into the phosphorylation-targeted Tyr of STAT1 enables light-regulated control of its phosphorylation, thus activating its transcriptional function. Furthermore, ncAA 30 has been incorporated into critical Tyr residues of various proteins, including Taq polymerase, imidazole glycerol phosphate synthase, and protein methyltransferase, enabling their functions to be photoregulated.…”

“…Its compact size is advantageous, as it facilitates the identification of engineered aaRSs capable of incorporating ncAAs that contain the nitrobenzyl group. Considering these advantages, ncAAs containing the nitrobenzyl group, derived from Tyr, − Lys, ,− Cys, − Ser, Asp, Glu, and His, have been incorporated into proteins using GCE technology to regulate protein functions. Recent advances have led to the development of many derivatives with improved stability and photoreactivity, thereby overcoming the limitations of the nitrobenzyl group. ,, …”