Catalytic mechanisms and specificities of glutathione peroxidases: Variations of a basic scheme

Stefano Toppo, Leopold Flohé, Fulvio Ursini, Stefano Vanin, Matilde Maiorino

Research output: Contribution to journalReview article

220 Citations (Scopus)

Abstract

Kinetics and molecular mechanisms of GPx-type enzymes are reviewed with emphasis on structural features relevant to efficiency and specificity. In Sec-GPxs the reaction takes place at a single redox centre with selenocysteine as redox-active residue (peroxidatic Sec, UP). In contrast, most of the non-vertebrate GPx have the UP replaced by a cysteine (peroxidatic Cys, CP) and work with a second redox centre that contains a resolving cysteine (CR). While the former type of enzymes is more or less specific for GSH, the latter are reduced by "redoxins". The common denominator of the GPx family is the first redox centre comprising the (seleno)cysteine, tryptophan, asparagine and glutamine. In this architectural context the rate of hydroperoxide reduction by UP or CP, respectively, is enhanced by several orders of magnitude compared to that of free selenolate or thiolate. Mammalian GPx-1 dominates H2O2 metabolism, whereas the domain of GPx-4 is the reduction of lipid hydroperoxides with important consequences such as counteracting 12/15-lipoxygenase-induced apoptosis and regulation of inflammatory responses. Beyond, the degenerate GSH specificity of GPx-4 allows selenylation and oxidation to disulfides of protein thiols. Heterodimer formation of yeast GPx with a transcription factor is discussed as paradigm of a redox sensing that might also be valid in vertebrates.

Original languageEnglish
Pages (from-to)1486-1500
Number of pages15
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number11
Early online date17 Apr 2009
DOIs
Publication statusPublished - Nov 2009
Externally publishedYes

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