Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway

Angew Chem Int Ed Engl. 2015 Feb 23;54(9):2821-4. doi: 10.1002/anie.201410045. Epub 2015 Jan 16.

Abstract

The non-heme iron enzyme EgtB catalyzes O2 -dependent C-S bond formation between γ-glutamyl cysteine and N-α-trimethyl histidine as the central step in ergothioneine biosynthesis. Both, the catalytic activity and the architecture of EgtB are distinct from known sulfur transferases or thiol dioxygenases. The crystal structure of EgtB from Mycobacterium thermoresistibile in complex with γ-glutamyl cysteine and N-α-trimethyl histidine reveals that the two substrates and three histidine residues serve as ligands in an octahedral iron binding site. This active site geometry is consistent with a catalytic mechanism in which C-S bond formation is initiated by an iron(III)-complexed thiyl radical attacking the imidazole ring of N-α-trimethyl histidine.

Keywords: enzyme catalysis; ergothioneine; non-heme iron enzymes; ovothiol; sulfur transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Biosynthetic Pathways*
  • Ergothioneine / biosynthesis*
  • Ergothioneine / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Oxidoreductases Acting on Sulfur Group Donors / chemistry*
  • Oxidoreductases Acting on Sulfur Group Donors / metabolism

Substances

  • Ergothioneine
  • Oxidoreductases Acting on Sulfur Group Donors