Trametes versicolor glutathione transferase Xi 3, a dual Cys-GST with catalytic specificities of both Xi and Omega classes

FEBS Lett. 2018 Sep;592(18):3163-3172. doi: 10.1002/1873-3468.13224. Epub 2018 Sep 6.

Abstract

Glutathione transferases (GSTs) from the Xi and Omega classes have a catalytic cysteine residue, which gives them reductase activities. Until now, they have been assigned distinct substrates. While Xi GSTs specifically reduce glutathionyl-(hydro)quinones, Omega GSTs are specialized in the reduction of glutathionyl-acetophenones. Here, we present the biochemical and structural analysis of TvGSTX1 and TvGSTX3 isoforms from the wood-degrading fungus Trametes versicolor. TvGSTX1 reduces GS-menadione as expected, while TvGSTX3 reduces both Xi and Omega substrates. An in-depth structural analysis indicates a broader active site for TvGSTX3 due to specific differences in the nature of the residues situated in the C-terminal helix α9. This feature could explain the catalytic duality of TvGSTX3. Based on phylogenetic analysis, we propose that this duality might exist in saprophytic fungi and ascomycetes.

Keywords: crystallography; dual enzyme activity; glutathione transferase Xi; glutathionyl-acetophenone reductase; glutathionyl-hydroquinone reductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biocatalysis
  • Crystallography, X-Ray
  • Cysteine / chemistry
  • Cysteine / genetics
  • Cysteine / metabolism*
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Glutathione / analogs & derivatives
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Glutathione Transferase / classification
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism*
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Models, Molecular
  • Phylogeny
  • Protein Binding
  • Protein Domains
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Trametes / enzymology*
  • Trametes / genetics

Substances

  • Fungal Proteins
  • Isoenzymes
  • Glutathione Transferase
  • Glutathione
  • Cysteine

Associated data

  • GENBANK/Tv66368
  • PDB/3PPU
  • PDB/6GC9
  • PDB/6GCA
  • PDB/6GCB
  • PDB/6GCC