The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Evolutionary and Structural Insights Into the Multifaceted Glutathione Peroxidase (Gpx) Superfamily
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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The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders
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Metadata
- Authors
- Toppo, S., Vanin, S., Bosello, V., & Tosatto, S. C. E.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2008-09
- Volume
- 10
- Issue
- 9
- Pages
- 1501-1514
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W1983311902
- Cited by
- 259
- References
- 65
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- closed
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- Toppo, S., Vanin, S., Bosello, V., & Tosatto, S. C. E. (2008). Evolutionary and Structural Insights Into the Multifaceted Glutathione Peroxidase (Gpx) Superfamily. Antioxidants & Redox Signaling. https://doi.org/10.1089/ars.2008.2057
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