LysargiNase mirrors trypsin for protein C-terminal and methylation-site identification

Nat Methods. 2015 Jan;12(1):55-8. doi: 10.1038/nmeth.3177. Epub 2014 Nov 24.


To improve proteome coverage and protein C-terminal identification, we characterized the Methanosarcina acetivorans thermophilic proteinase LysargiNase, which cleaves before lysine and arginine up to 55 °C. Unlike trypsin, LysargiNase-generated peptides had N-terminal lysine or arginine residues and fragmented with b ion-dominated spectra. This improved protein C terminal-peptide identification and several arginine-rich phosphosite assignments. Notably, cleavage also occurred at methylated or dimethylated lysine and arginine, facilitating detection of these epigenetic modifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Metalloproteases / metabolism*
  • Methanosarcina / enzymology
  • Methylation
  • Protein Processing, Post-Translational
  • Proteome / metabolism
  • Proteomics / methods*
  • Substrate Specificity
  • Trypsin / metabolism


  • Proteome
  • Metalloproteases
  • ulilysin, Methanosarcina acetivorans
  • Trypsin