Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level.
PMID 31123777 · Cellular and molecular life sciences : CMLS · 2019 · DOI 10.1007/s00018-019-03145-x
Authors: Sunil Kumar Tewary; Y George Zheng; Meng-Chiao Ho
Abstract
Protein arginine methyltransferases (PRMTs) catalyze the methyl transfer to the arginine residues of protein substrates and are classified into three major types based on the final form of the methylated arginine. Recent studies have shown a strong correlation between PRMT expression level and the prognosis of cancer patients. Currently, crystal structures of eight PRMT members have been determined. Kinetic and structural studies have shown that all PRMTs share similar, but unique catalytic and substrate recognition mechanism. In this review, we discuss the structural similarities and differences of different PRMT members, focusing on their overall structure, S-adenosyl-L-methionine-binding pocket, substrate arginine recognition and catalytic mechanisms. Since PRMTs are valuable targets for drug discovery, we also rationally classify the known PRMT inhibitors into five classes and discuss their mechanisms of action at the atomic level.
Arginine; Binding Sites; Catalytic Domain; Enzyme Inhibitors; Humans; Methylation; Protein Isoforms; Protein-Arginine N-Methyltransferases; Substrate Specificity
Cite
Sunil Kumar Tewary; Y George Zheng; Meng-Chiao Ho. Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level. Cellular and molecular life sciences : CMLS (2019). PMID 31123777. DOI 10.1007/s00018-019-03145-x.