A remodeled protein arginine methyltransferase 1 (PRMT1) generates symmetric dimethylarginine

Shanying Gui, Symon Gathiaka, Jun Li, Jun Qu, Orlando Acevedo, Joan M. Hevel

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Protein arginine methylation is emerging as a significant post-translational modification involved in various cell processes and human diseases. As the major arginine methylation enzyme, protein arginine methyltransferase 1 (PRMT1) strictly generates monomethylarginine and asymmetric dimethylarginine (ADMA), but not symmetric dimethylarginine (SDMA). The two types of dimethylarginines can lead to distinct biological outputs, as highlighted in the PRMT-dependent epigenetic control of transcription. However, it remains unclear how PRMT1 product specificity is regulated. We discovered that a single amino acid mutation (Met-48 to Phe) in the PRMT1 active site enables PRMT1 to generate bothADMAand SDMA. Due to the limited amount of SDMA formed, we carried out quantum mechanical calculations to determine the free energies of activation of ADMA and SDMA synthesis. Our results indicate that the higher energy barrier ofSDMAformation (ΔΔG‡ = 3.2 kcal/mol as compared with ADMA) may explain the small amount of SDMA generated by M48F-PRMT1. Our study reveals unique energetic challenges for SDMA-forming methyltransferases and highlights the exquisite control of product formation by active site residues in the PRMTs.

Original languageEnglish (US)
Pages (from-to)9320-9327
Number of pages8
JournalJournal of Biological Chemistry
Issue number13
StatePublished - Mar 30 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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