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

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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.

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Acknowledgements

S.K.T. was supported by Taiwan Protein Project (Grant no. AS-KPQ-105-TPP). Y.G.Z. was supported by NIH Grant R01GM126154. M.C.H. was supported by the Academia Sinica and Ministry of Science and Technology (MOST 107-2311-B-001-002).

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Authors and Affiliations

  1. Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan

    Sunil Kumar Tewary & Meng-Chiao Ho

  2. College of Pharmacy, University of Georgia, Athens, GA, 30602, USA

    Y. George Zheng

  3. Institute of Biochemical Sciences, National Taiwan University, Taipei, 106, Taiwan

    Meng-Chiao Ho

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  1. Sunil Kumar Tewary
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  2. Y. George Zheng
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  3. Meng-Chiao Ho
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Correspondence to Meng-Chiao Ho.

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Tewary, S.K., Zheng, Y.G. & Ho, MC. Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level. Cell. Mol. Life Sci. 76, 2917–2932 (2019). https://doi.org/10.1007/s00018-019-03145-x

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