A possible S-glutathionylation of specific proteins by glyoxalase II: An in vitro and in silico study

Cell Biochem Funct. 2016 Dec;34(8):620-627. doi: 10.1002/cbf.3236.

Abstract

Glyoxalase II, the second of 2 enzymes in the glyoxalase system, is a hydroxyacylglutathione hydrolase that catalyses the hydrolysis of S-d-lactoylglutathione to form d-lactic acid and glutathione, which is released from the active site. The tripeptide glutathione is the major sulfhydryl antioxidant and has been shown to control several functions, including S-glutathionylation of proteins. S-Glutathionylation is a way for the cells to store reduced glutathione during oxidative stress, or to protect protein thiol groups from irreversible oxidation, and few enzymes involved in protein S-glutathionylation have been found to date. In this work, the enzyme glyoxalase II and its substrate S-d-lactoylglutathione were incubated with malate dehydrogenase or with actin, resulting in a glutathionylation reaction. Glyoxalase II was also submitted to docking studies. Computational data presented a high propensity of the enzyme to interact with malate dehydrogenase or actin through its catalytic site and further in silico investigation showed a high folding stability of glyoxalase II toward its own reaction product glutathione both protonated and unprotonated. This study suggests that glyoxalase II, through a specific interaction of its catalytic site with target proteins, could be able to perform a rapid and specific protein S-glutathionylation using its natural substrate S-d-lactoylglutathione.

Significance: This article reports for the first time a possible additional role of Glo2 that, after interacting with a target protein, is able to promote S-glutathionylation using its natural substrate SLG, a glutathione derived compound. In this perspective, Glo2 can play a new important regulatory role inS-glutathionylation, acquiring further significance in cellular post-translational modifications of proteins.

Keywords: Glyoxalase II; MDH protein; S-d-lactoylglutathione; actin protein; glutathione; glutathionylation; glyoxalase system; post-translational modification (PTM).

MeSH terms

  • Actins / metabolism
  • Computer Simulation*
  • Glutathione / chemistry
  • Glutathione / metabolism*
  • Humans
  • Malate Dehydrogenase / metabolism
  • Molecular Docking Simulation
  • Thiolester Hydrolases / chemistry
  • Thiolester Hydrolases / metabolism*

Substances

  • Actins
  • Malate Dehydrogenase
  • Thiolester Hydrolases
  • hydroxyacylglutathione hydrolase
  • Glutathione