Structural analysis of HmtT and HmtN involved in the tailoring steps of himastatin biosynthesis

FEBS Lett. 2013 Jun 5;587(11):1675-80. doi: 10.1016/j.febslet.2013.04.013. Epub 2013 Apr 20.


Himastatin is a novel antibiotic featuring a bicyclohexadepsipeptide structure. On the himastatin biosynthesis pathway, three cytochrome P450s (HmtT, HmtN, HmtS) are responsible for the post-tailoring of the cyclohexadepsipeptide backbone. Here we report the crystal structures of HmtT and HmtN. The overall structures of these two proteins are homologous to other cytochrome P450s. However, the exceptionally long F-G loop in HmtT has a highly unusual conformation and extends deep into the active site. As a result, the F/G helices of HmtT are both kinked. In contrast, the F/G helices of HmtN are straight. Also, the F/G helices in HmtT and HmtN take distinctive orientations, which may be a contributing factor for the substrate specificity of these two enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Catalytic Domain
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cytochrome P-450 Enzyme System / chemistry*
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Peptides, Cyclic
  • Protein Structure, Secondary
  • Streptomyces / enzymology*
  • Structural Homology, Protein


  • Bacterial Proteins
  • Peptides, Cyclic
  • himastatin
  • Cytochrome P-450 Enzyme System

Associated data

  • PDB/4E2P
  • PDB/4GGV