PGP: A drug target (or biomarker) for Aspartate-based ubiquitous Mg(2+)-dependent phosphatase

Target Name: PGP

NCBI ID: G283871

Content of Review Report on PGP Target / Biomarker

PGP

PGP: A drug target (or biomarker) for Aspartate-based ubiquitous Mg(2+)-dependent phosphatase

Introduction

Phosphatases are a class of enzymes that regulate the phosphate groups on target proteins, thereby participating in various cellular processes. Aspartate-based ubiquitous Mg(2+)-dependent phosphatases (PGPs) have been identified as potential drug targets or biomarkers due to their unique mechanism of action and diverse functions in various cellular processes. In this article, we will discuss the biology, structure, and potential drug targets of PGP.

Structure and Mechanism

PGPs are a subclass of phosphatases that use aspartate as a catalytic center. These enzymes belong to different families, such as the N-type ATPases (NATs), the Mg2+-dependent ATPases (MDAPs), and the C-type ATPases (CTAPs) . PGP functions include regulating protein-protein interactions, DNA replication, and cell signaling pathways.

PGPs can be divided into two distinct subclasses:

1. Aspartate-based ubiquitous Mg(2+)-dependent phosphatases (PGPs-UM): These enzymes use aspartate as the catalytic center and require Mg2+ ions as a cofactor to function. PGPs-UMs are widely distributed in various cellular compartments and play essential roles in various cellular processes, including intracellular signaling, DNA replication, and protein-protein interactions. Promoters of PGPs-UMs often contain multiple aspartate residues that can serve as electrodes for Mg2+ ions.
2. Aspartate-based ubiquitous Mg(2+)-independent phosphatases (PGPs-IN): These enzymes use aspartate as the catalytic center but do not require Mg2+ ions as a cofactor. PGPs-INs are involved in various cellular processes, including intracellular signaling, DNA replication, and protein-protein interactions. Promoters of PGPs-INs often contain a single aspartate residue that can serve as an electrode for Mg2+ ions.

PGPs have unique properties due to their Aspartate-based architecture. Aspartate residues in PGP catalytic centers are highly conserved and often have an imidazole ring structure. This imidazole ring is crucial for the stability and redox properties of the enzyme. Additionally, PGP catalytic centers are usually protonated, which allows them to serve as electrodes for Mg2+ ions.

PGPs function in various cellular processes by regulating protein-protein interactions and controlling the levels of intracellular signaling pathways. They play a key role in intracellular signaling by modulating the activity of various enzymes and modulating the expression of target genes. For instance, PGPs can regulate the activity of enzymes involved in cell signaling pathways, such as tyrosine kinases, G-protein-coupled receptors, and ion channels.

PGPs have been identified as potential drug targets due to their unique mechanism of action and diverse functions. They can be inhibited by small molecules, such as inhibitors of the imidazole ring or inhibitors of the protonation state. In addition, PGPs can be used as biomarkers for various diseases, such as cancer, neurodegenerative diseases, and autoimmune diseases.

Drug Development and Optimization

Several small molecules have been identified as potential inhibitors of PGP. These molecules act by modulating the activity of PGP, either by inhibiting the imidazole ring or by blocking the protonation state. One of the most promising molecules is a peptide called GF1012, which is derived from a crabby sea spider venom.

GF1012 was shown to inhibit the activity of PGP

Protein Name: Phosphoglycolate Phosphatase

Functions: Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-phosphate into glycerol. Thereby, regulates the cellular levels of glycerol-3-phosphate a metabolic intermediate of glucose, lipid and energy metabolism. Was also shown to have a 2-phosphoglycolate phosphatase activity and a tyrosine-protein phosphatase activity. However, their physiological relevance is unclear (PubMed:26755581). In vitro, has also a phosphatase activity toward ADP, ATP, GDP and GTP (By similarity)

The "PGP Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about PGP comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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