The structure of Lactococcus lactis thioredoxin reductase reveals molecular features of photo-oxidative damage

Sci Rep. 2017 Apr 11;7:46282. doi: 10.1038/srep46282.


The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD generating superoxide and a flavin radical that oxidize the isoalloxazine ring C7α methyl group and a nearby tyrosine residue. This tyrosine and key residues surrounding the oxygen pocket are conserved in enzymes from related bacteria, including pathogens such as Staphylococcus aureus. Photo-sensitivity may thus be a widespread feature among bacterial TrxR with the described characteristics, which affords applications in clinical photo-therapy of drug-resistant bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Flavin-Adenine Dinucleotide / metabolism
  • Flavins / chemistry
  • Flavins / metabolism
  • Lactococcus lactis / enzymology*
  • Lactococcus lactis / radiation effects*
  • Light*
  • Metabolic Networks and Pathways
  • Models, Molecular
  • Molecular Conformation
  • Oxidation-Reduction
  • Oxidative Stress*
  • Photochemical Processes*
  • Structure-Activity Relationship
  • Thioredoxin-Disulfide Reductase / chemistry*
  • Thioredoxin-Disulfide Reductase / metabolism*


  • Flavins
  • Flavin-Adenine Dinucleotide
  • isoalloxazine
  • Thioredoxin-Disulfide Reductase