Structural evidence for conformational changes of Delta class glutathione transferases after ligand binding

Arch Biochem Biophys. 2012 May;521(1-2):77-83. doi: 10.1016/j.abb.2012.03.023. Epub 2012 Mar 27.

Abstract

We report four new crystal structures for Delta class glutathione transferases from insects. We compare these new structures as well as several previously reported structures to determine that structural transitions can be observed with ligand binding. These transitions occurred in the regions around the active site entrance, including alpha helix 2, C-terminus of alpha helix 4 including the loop to helix 5 and the C-terminus of helix 8. These structural movements have been reported or postulated to occur for several other glutathione transferase classes; however, this is the first report showing structural evidence of all these movements occurring, in this case in Delta class glutathione transferases. These fluctuations also can be observed occurring within a single structure as there is ligand bound in only one subunit and each subunit is undergoing different conformational transitions. The structural comparisons show reorganizations occur both pre- and post-GSH ligand binding communicated through the subunit interface of the quaternary assembly. Movements of these positions would allow 'breathing' of the active site for substrate entrance, topological rearrangement for varying substrate specificity and final product release.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Crystallography, X-Ray
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / classification
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Glutathione Transferase / chemistry*
  • Glutathione Transferase / classification
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism*
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Protein Subunits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity

Substances

  • Drosophila Proteins
  • Ligands
  • Protein Subunits
  • Recombinant Proteins
  • Glutathione Transferase