title: A possible S-glutathionylation of specific proteins by glyoxalase II: An in vitro and in silico study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ercolani
authors.affiliation: Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scirè
authors.affiliation: Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Galeazzi
authors.affiliation: Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Massaccesi
authors.affiliation: Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cianfruglia
authors.affiliation: Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Amici
authors.affiliation: Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piva
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, Università di Perugia, Perugia, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Urbanelli
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, Università di Perugia, Perugia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
authors.affiliation: Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Principato
authors.affiliation: Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Tatiana
authors.identifier: http://orcid.org/0000-0003-0931-1342
authors.initials: T
authors.lastname: Armeni
mesh_terms: D000199:Actins / Q000378:metabolism; D003198:Computer Simulation; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008291:Malate Dehydrogenase / Q000378:metabolism; D062105:Molecular Docking Simulation; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D000199:Actins; D005978:Glutathione; D008291:Malate Dehydrogenase; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase
keywords: Glyoxalase II; MDH protein; S-d-lactoylglutathione; actin protein; glutathione; glutathionylation; glyoxalase system; post-translational modification (PTM)