Evolutionary and Structural Insights Into the Multifaceted Glutathione Peroxidase (Gpx) Superfamily
Publication: Antioxidants & Redox Signaling
Volume 10, Issue Number 9
Abstract
Glutathione peroxidase (GPx) is a widespread protein superfamily found in many organisms throughout all kingdoms of life. Although it was initially thought to use only glutathione as reductant, recent evidence suggests that the majority of GPxs have specificity for thioredoxin. We present a thorough in silico analysis performed on 724 sequences and 12 structures aimed to clarify the evolutionary, structural, and sequence determinants of GPx specificity. Structural variability was found to be limited to only two regions, termed oligomerization loop and functional helix, which modulate both reduced substrate specificity and oligomerization state. We show that mammalian GPx-1, the canonic selenocysteine-based tetrameric glutathione peroxidase, is a recent “invention” during evolution. Contrary to common belief, cysteine-based thioredoxin-specific GPx, which we propose the TGPx, are both more common and more ancient. This raises interesting evolutionary considerations regarding oligomerization and the use of active-site selenocysteine residue. In addition, phylogenetic analysis has revealed the presence of a novel member belonging to the GPx superfamily in Mammalia and Amphibia, for which we propose the name GPx-8, following the present numeric order of the mammalian GPxs.
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Published In
Antioxidants & Redox Signaling
Volume 10 • Issue Number 9 • September 2008
Pages: 1501 - 1514
PubMed: 18498225
Copyright
Mary Ann Liebert, Inc.
History
Published in print: September 2008
Published online: 3 July 2008
Published ahead of print: 22 May 2008
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