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Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site
Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621891/ https://www.ncbi.nlm.nih.gov/pubmed/23593192 http://dx.doi.org/10.1371/journal.pone.0060324 |
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author | Brock, Joseph Board, Philip G. Oakley, Aaron J. |
author_facet | Brock, Joseph Board, Philip G. Oakley, Aaron J. |
author_sort | Brock, Joseph |
collection | PubMed |
description | Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot of the enzyme in the process of regeneration. GSSG occupies both the G (GSH-binding) and H (hydrophobic-binding) sites and causes re-arrangement of some H-site residues. In the same structure we demonstrate the existence of a novel “ligandin” binding site deep within in the dimer interface of this enzyme, containing S-(4-nitrophenacyl)glutathione, an isozyme-specific substrate for hGSTO1-1. The ligandin site, conserved in Omega class GSTs from a range of species, is hydrophobic in nature and may represent the binding location for tocopherol esters that are uncompetitive hGSTO1-1 inhibitors. |
format | Online Article Text |
id | pubmed-3621891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36218912013-04-16 Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site Brock, Joseph Board, Philip G. Oakley, Aaron J. PLoS One Research Article Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot of the enzyme in the process of regeneration. GSSG occupies both the G (GSH-binding) and H (hydrophobic-binding) sites and causes re-arrangement of some H-site residues. In the same structure we demonstrate the existence of a novel “ligandin” binding site deep within in the dimer interface of this enzyme, containing S-(4-nitrophenacyl)glutathione, an isozyme-specific substrate for hGSTO1-1. The ligandin site, conserved in Omega class GSTs from a range of species, is hydrophobic in nature and may represent the binding location for tocopherol esters that are uncompetitive hGSTO1-1 inhibitors. Public Library of Science 2013-04-09 /pmc/articles/PMC3621891/ /pubmed/23593192 http://dx.doi.org/10.1371/journal.pone.0060324 Text en © 2013 Brock et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Brock, Joseph Board, Philip G. Oakley, Aaron J. Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site |
title | Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site |
title_full | Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site |
title_fullStr | Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site |
title_full_unstemmed | Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site |
title_short | Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of a Non-Catalytic Ligandin Site |
title_sort | structural insights into omega-class glutathione transferases: a snapshot of enzyme reduction and identification of a non-catalytic ligandin site |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621891/ https://www.ncbi.nlm.nih.gov/pubmed/23593192 http://dx.doi.org/10.1371/journal.pone.0060324 |
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