Molecular modeling of the catalytic domain of serine/threonine phosphatase-1 with the Zn2+ and Mn2+ di-nuclear ion centers in the active site

Woźniak, Edyta; Ołdziej, Stanisław; Ciarkowski, Jerzy

doi:10.1016/s0097-8485(99)00079-0

Cited by 11 publications

(10 citation statements)

References 26 publications

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“…The C subunit embodies a globular structure with an α/β fold. This structure is homologous to other PPP catalytic subunits; however, the subunits are not interchangeable among the different enzyme types . The molecular basis for these interactions was described when the AC dimer, also known as the ‘core enzyme’, crystal structure was solved .…”

Section: Structural Contributions To Pp2a Activitymentioning

confidence: 99%

All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase

et al. 2015

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Protein phosphatase 2A is a serine/threonine phosphatase involved in the regulation of many cellular processes. A confirmed tumor suppressor protein, PP2A is genetically altered or functionally inactivated in many cancers highlighting a need for its therapeutic reactivation. In this review we will discuss recent literature on PP2A: the elucidation of its structure and the functions of its subunits, and the identification of molecular lesions and post-translational modifications leading to its dysregulation in cancer. A final section will discuss the proteins and small molecules that modulate PP2A and how these might be used to target dysregulated forms of PP2A to treat cancers and other diseases.

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Section: Structural Contributions To Pp2a Activitymentioning

confidence: 99%

All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase

et al. 2015

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“…These associated proteins either function as targeting subunits, which guide PP1 to its substrate and to the desired subcellular location or regulate its catalytic activity (11). Importantly, it has also been suggested that these targeting subunits stabilize PP1 and prevent its degradation (12). The regulation of PP1 by its auxiliary proteins at the level of the SR is described in Section 5.…”

Section: Type 1 Protein Phosphatase (Pp1)mentioning

confidence: 99%

Role of PP1 in the regulation of Ca cycling in cardiac physiology and pathophysiology

Nicolaou

Kranias²

2009

Front Biosci

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Type 1 protein phosphatase (PP1) is a critical regulator of several cellular processes. In the heart, it mediates restoration of contractility to basal levels by dephosphorylating key phospho-proteins, after beta-adrenergic stimulation. PP1 is a holoenzyme consisting of its catalytic and regulatory subunits. The regulatory proteins anchor the catalytic subunit to desired subcellular locations, define substrate specificity and modulate catalytic activity. At the level of the cardiac sarcoplasmic reticulum (SR), PP1 is regulated by two endogenous inhibitors, Inhibitor-1 (I-1) and Inhibitor-2 (I-2), which modulate its activity according to cellular conditions. In addition, the striated muscle-specific glycogen-targeting subunit, GM/RGL, targets PP1 to the SR vicinity. Regulation of PP1 activity is highly important in maintaining proper cardiac function under physiological conditions. In fact, aberrant Ca handling and depressed contractility, observed in human and experimental heart failure, have been at least partly attributed to increases in the catalytic activity of PP1, mediated by impaired regulation via its endogenous inhibitors. Importantly, increases in the level and activity of I-1 and I-2 in animal models have been successful in ameliorating the cardiac dysfunction and remodeling in heart failure, suggesting that PP1 inhibition may be a plausible therapeutic strategy to alleviate the detrimental manifestations of heart failure.

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“…1). The crystal structure of mammalian PP1c revealed that PP1 is a metalloenzyme with two divalent metal ions at the center of the catalytic site, Fe 2+ and Zn 2+ are the most plausible ions in the native enzymes [14,15]. Most PP1 regulatory subunits interact with the PP1 catalytic subunit through a conserved PP1 binding motif termed the RVxF motif.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Protein phosphatase 1 is a key player in nuclear events

Rebelo

Santos

Martins

et al. 2015

Cellular Signalling

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Molecular modeling of the catalytic domain of serine/threonine phosphatase-1 with the Zn2+ and Mn2+ di-nuclear ion centers in the active site

Cited by 11 publications

References 26 publications

All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase

All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase

Role of PP1 in the regulation of Ca cycling in cardiac physiology and pathophysiology

Protein phosphatase 1 is a key player in nuclear events

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