ArticleBiochemistry2013
Binding of a third metal ion by the human phosphatases PP2Cα and Wip1 is required for phosphatase activity.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Sarbecoviruses Suppress Innate Immunity by Recruiting PPM1A to Modulate STAT2 and ORF9b Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Article
- PPM1B utilizes a trinuclear metal architecture for phosphatase activity.bioRxiv : the preprint server for biology · 2026Article
- PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Protein phosphatase PP2C19 controls hypocotyl phototropism through the phosphorylation modification of NONPHOTOTROPIC HYPOCOTYL3 in Arabidopsis.Plant & cell physiology · 2025Article
- Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation.bioRxiv : the preprint server for biology · 2024Article
- Alkyl-substituted N-methylaryl-N'-aryl-4-aminobenzamides: A new series of small molecule inhibitors for Wip1 phosphatase.European journal of medicinal chemistry · 2022Article
- Discovery of Novel Small-Molecule Scaffolds for the Inhibition and Activation of WIP1 Phosphatase from a RapidFire Mass Spectrometry High-Throughput Screen.ACS pharmacology & translational science · 2022Article
- Review
- Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PMInternational journal of molecular sciences · 2022Article
- The SiaABC threonine phosphorylation pathway controls biofilm formation in response to carbon availability in Pseudomonas aeruginosa.PloS one · 2020Article
- PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins.eLife · 2019Article
- A trapped human PPM1A-phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity.The Journal of biological chemistry · 2018Article
- Chemical Features Important for Activity in a Class of Inhibitors Targeting the Wip1 Flap Subdomain.ChemMedChem · 2018Article
- Conformational Changes in Active and Inactive States of Human PP2Cα Characterized by Hydrogen/Deuterium Exchange-Mass Spectrometry.Biochemistry · 2017Article
- CTL0511 from Chlamydia trachomatis Is a Type 2C Protein Phosphatase with Broad Substrate Specificity.Journal of bacteriology · 2016Article
- Structural Mechanism Underlying the Specific Recognition between the Arabidopsis State-Transition Phosphatase TAP38/PPH1 and Phosphorylated Light-Harvesting Complex Protein Lhcb1.The Plant cell · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The PPM phosphatases require millimolar concentrations of Mg²⁺ or Mn²⁺ to activate phosphatase activity in vitro. The human phosphatases PP2Cα (PPM1A) and Wip1 (PPM1D) differ in their physiological function, substrate specificity, and apparent metal affinity. A crystallographic structure of PP2Cα shows only two metal ions in the active site. However, recent structural studies of several bacterial PP2C phosphatases have indicated three metal ions in the active site. Two residues that coordinate the third metal ion are highly conserved, suggesting that human PP2C phosphatases may also bind a third ion. Here, isothermal titration calorimetry analysis of Mg²⁺ binding to PP2Cα distinguished binding of two ions to high affinity sites from the binding of a third ion with a millimolar affinity, similar to the apparent metal affinity required for catalytic activity. Mutational analysis indicated that Asp239 and either Asp146 or Asp243 was required for low-affinity binding of Mg²⁺, but that both Asp146 and Asp239 were required for catalysis. Phosphatase activity assays in the presence of MgCl₂, MnCl₂, or mixtures of the two, demonstrate high phosphatase activity toward a phosphopeptide substrate when Mg²⁺ was bound to the low-affinity site, whether Mg²⁺ or Mn²⁺ ions were bound to the high affinity sites. Mutation of the corresponding putative third metal ion-coordinating residues of Wip1 affected catalytic activity similarly both in vitro and in human cells. These results suggest that phosphatase activity toward phosphopeptide substrates by PP2Cα and Wip1 requires the binding of a Mg²⁺ ion to the low-affinity site.
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Registered trials
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