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Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins
Phosphoprotein phosphatases (PPPs) are a ubiquitous class of enzymes which dephosphorylate serine and threonine residues on substrate proteins involved in a wide variety of cellular processes. The active site of PPP enzymes are highly conserved with key residues coordinating the substrate phosphoryl...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214084/ https://www.ncbi.nlm.nih.gov/pubmed/37144562 http://dx.doi.org/10.1042/BSR20230378 |
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author | Kerk, David White-Gloria, Chris Johnson, Jayde J. Moorhead, Greg B. |
author_facet | Kerk, David White-Gloria, Chris Johnson, Jayde J. Moorhead, Greg B. |
author_sort | Kerk, David |
collection | PubMed |
description | Phosphoprotein phosphatases (PPPs) are a ubiquitous class of enzymes which dephosphorylate serine and threonine residues on substrate proteins involved in a wide variety of cellular processes. The active site of PPP enzymes are highly conserved with key residues coordinating the substrate phosphoryl group (the two R-clamp) and two metal ions necessary for catalysis. Because of the diverse number of roles that these enzymes play it is no surprise that they are highly regulated in the cell, often accomplished by binding regulatory subunits. These regulatory subunits are able to dictate substrate specificity, localization, and activity of the bound catalytic subunit. Eukaryotic PPP subtypes have been previously shown to manifest varying degrees of sensitivity to environmental toxins. We present here an evolutionary model which now rationalizes this data. Our re-examination of published structural evidence reveals that Eukaryotic PPP toxin-binding residues also interact with substrate binding residues (the two R-clamp) and ancient regulatory proteins. Such functional interactions could have stabilized PPP sequence early in Eukaryotic evolution, providing a stable target which was co-opted by toxins and their producer organisms. |
format | Online Article Text |
id | pubmed-10214084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102140842023-05-27 Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins Kerk, David White-Gloria, Chris Johnson, Jayde J. Moorhead, Greg B. Biosci Rep Bioinformatics Phosphoprotein phosphatases (PPPs) are a ubiquitous class of enzymes which dephosphorylate serine and threonine residues on substrate proteins involved in a wide variety of cellular processes. The active site of PPP enzymes are highly conserved with key residues coordinating the substrate phosphoryl group (the two R-clamp) and two metal ions necessary for catalysis. Because of the diverse number of roles that these enzymes play it is no surprise that they are highly regulated in the cell, often accomplished by binding regulatory subunits. These regulatory subunits are able to dictate substrate specificity, localization, and activity of the bound catalytic subunit. Eukaryotic PPP subtypes have been previously shown to manifest varying degrees of sensitivity to environmental toxins. We present here an evolutionary model which now rationalizes this data. Our re-examination of published structural evidence reveals that Eukaryotic PPP toxin-binding residues also interact with substrate binding residues (the two R-clamp) and ancient regulatory proteins. Such functional interactions could have stabilized PPP sequence early in Eukaryotic evolution, providing a stable target which was co-opted by toxins and their producer organisms. Portland Press Ltd. 2023-05-23 /pmc/articles/PMC10214084/ /pubmed/37144562 http://dx.doi.org/10.1042/BSR20230378 Text en © 2023 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Bioinformatics Kerk, David White-Gloria, Chris Johnson, Jayde J. Moorhead, Greg B. Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins |
title | Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins |
title_full | Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins |
title_fullStr | Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins |
title_full_unstemmed | Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins |
title_short | Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins |
title_sort | eukaryotic-like phosphoprotein phosphatase (ppp) enzyme evolution: interactions with environmental toxins and regulatory proteins |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214084/ https://www.ncbi.nlm.nih.gov/pubmed/37144562 http://dx.doi.org/10.1042/BSR20230378 |
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