Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2

FEBS Lett. 2013 Nov 29;587(23):3859-68. doi: 10.1016/j.febslet.2013.10.020.


SUV420H1 and SUV420H2 are two highly homologous enzymes that methylate lysine 20 of histone H4 (H4K20), a mark that has been implicated in transcriptional regulation. In this study, we present the high-resolution crystal structures of human SUV420H1 and SUV420H2 in complex with SAM, and report their substrate specificity. Both methyltransferases have a unique N-terminal domain and Zn-binding post-SET domain, and prefer the monomethylated histone H4K20 as a substrate in vitro. No histone H4K20 trimethylation activity was detected by our radioactivity-based assay for either enzyme, consistent with the presence of a conserved serine residue that forms a hydrogen bond with the target lysine side-chain and limits the methylation level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Histone-Lysine N-Methyltransferase / chemistry*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism*
  • Humans
  • Methylation
  • Molecular Docking Simulation
  • Molecular Sequence Data
  • Mutation
  • S-Adenosylmethionine / chemistry
  • S-Adenosylmethionine / metabolism
  • Substrate Specificity
  • Zinc / metabolism


  • Histones
  • S-Adenosylmethionine
  • Histone-Lysine N-Methyltransferase
  • KMT5C protein, human
  • Zinc