Human cytosolic glutathione transferases: structure, function, and drug discovery

Trends Pharmacol Sci. 2012 Dec;33(12):656-68. doi: 10.1016/j.tips.2012.09.007. Epub 2012 Oct 31.

Abstract

Glutathione transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of electrophilic substrates to glutathione. In recent years, GSTs have been of great interest in pharmacology and drug development because of their involvement in many important biological processes such as steroid and prostaglandin biosynthesis, tyrosine catabolism, and cell apoptosis. This review describes crystal structures for cytosolic GSTs and correlates active-site features with enzyme functions (e.g., steroid synthesis, tyrosine degradation, and dehydroascorbate reduction) and substrate selectivity. Use of these crystal structures for the design of specific inhibitors for several GST enzymes is also discussed.

Publication types

  • Review

MeSH terms

  • Crystallography, X-Ray
  • Cytosol / enzymology*
  • Drug Discovery
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glutathione Transferase / antagonists & inhibitors*
  • Glutathione Transferase / chemistry*
  • Glutathione Transferase / metabolism
  • Humans
  • Models, Molecular
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Glutathione Transferase