Structural characterization of the mitomycin 7-O-methyltransferase

Proteins. 2011 Jul;79(7):2181-8. doi: 10.1002/prot.23040. Epub 2011 May 2.


Mitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7-O-methylation of both C9β- and C9α-configured 7-hydroxymitomycins. We have determined the crystal structures of the MmcR-S-adenosylhomocysteine (SAH) binary complex and MmcR-SAH-mitomycin A (MMA) ternary complex at resolutions of 1.9and 2.3 Å, respectively. The study revealed MmcR to adopt a common S-adenosyl-L-methionine-dependent O-methyltransferase fold and the presence of a structurally conserved active site general acid-base pair is consistent with a proton-assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylation to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins
  • Binding Sites
  • Crystallography, X-Ray
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism
  • Mitomycin / chemistry*
  • Mitomycin / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • S-Adenosylhomocysteine / chemistry*
  • S-Adenosylhomocysteine / metabolism
  • Sequence Alignment
  • Streptomyces / enzymology
  • Structural Homology, Protein


  • Bacterial Proteins
  • Recombinant Proteins
  • Mitomycin
  • S-Adenosylhomocysteine
  • Methyltransferases