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Cell Mol Life Sci. 2019 Aug;76(15):2917-2932. doi: 10.1007/s00018-019-03145-x. Epub 2019 May 23.

Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level.

Author information

1
Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan.
2
College of Pharmacy, University of Georgia, Athens, GA, 30602, USA.
3
Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan. joeho@gate.sinica.edu.tw.
4
Institute of Biochemical Sciences, National Taiwan University, Taipei, 106, Taiwan. joeho@gate.sinica.edu.tw.

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.

KEYWORDS:

PRMT inhibitors; Product specificity; Protein arginine methyltransferase; Substrate arginine recognition

PMID:
31123777
DOI:
10.1007/s00018-019-03145-x

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