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...

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Bibliographic Details
Published in:Bioscience reports 2023-05, Vol.43 (5), p.1
Main Authors: Kerk, David, White-Gloria, Chris, Johnson, Jayde J, Moorhead, Greg Bruce
Format: Article
Language:English
Subjects:
Acids
Bacteria
Binding
Bioinformatics
Brief Report
Catalysis
Enzymes
Enzymology
Evolution
Evolutionary Biology
Kinases
Localization
Metal ions
Molecular Interactions
Omics
Phosphatase
Phosphoprotein phosphatase
Phosphorylation
Phylogenetics
Post-Translational Modifications
Proteins
Regulatory proteins
Regulatory sequences
Regulatory subunits
Residues
Substrate specificity
Substrates
Toxins
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Summary: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.
ISSN:0144-8463
1573-4935
DOI:10.1042/BSR20230378