Microsomal glutathione transferase 1: mechanism and functional roles

Abstract

Microsomal glutathione transferase 1 (MGST1) belongs to a superfamily named MAPEG (membrane-associated proteins in eicosanoid and glutathione metabolism). This family is represented in all life forms, except archae. Of the six human members, three are specialized in the synthesis of leukotrienes and prostaglandin E, whereas the others (MGST1–3) have potential roles in drug metabolism. MGST1 has a well-established role in the conjugation of electrophiles and oxidative stress protection, whereas MGST2 and 3 have been less studied. Here, we review the recent advances regarding the structure, mechanism, and functional roles of MGST1. Emerging data show that the enzyme is overexpressed in certain tumors and support a role for the enzyme in protecting cells from cytostatic drugs.

Keywords::

• Microsomal glutathione transferase
• structure-function
• mechanism
• fluorescent substrates
• expression
• drug resistance

Acknowledgments

The authors are grateful to Peter Holm, who prepared a template for Figures 1 and 2.

Declaration of interest

Studies in the author’s laboratory were supported by the Swedish Research Council and funds from Karolinska Institutet.