Phosphoglycolate phosphatase (PGP)

Phosphoglycolate phosphatase (PGP) is an **Mg(2+)-dependent enzyme** of the haloacid dehalogenase (HAD) superfamily that catalyzes the **hydrolysis of 2-phosphoglycolate to glycolate and phosphate**[2][1]. This reaction is essential for cellular metabolism in both plants and animals: in plants, PGP supports photosynthetic metabolism by detoxifying 2-phosphoglycolate produced during photorespiration, while in mammals and protozoa, it performs a **“metabolic proofreading”** function by removing toxic phosphorylated metabolites that otherwise inhibit core glycolytic enzymes and disrupt cellular function[3][5]. Structurally, PGP contains a Rossmannoid core and cap domain and requires Mg(2+) for catalysis[1][2]. Its active site includes conserved aspartate, lysine, and serine residues, typical of HAD superfamily enzymes[2]. PGP is crucial for cell viability in organisms such as Plasmodium species, highlighting its potential as a **therapeutic target in malaria**[5][4]. There is **currently no approved drug** targeting human PGP, but selective inhibitors of parasite PGP are being investigated as potential anti-malarials[5][4].

Other names

Glycerol-3-phosphate phosphataseG3PPAUMAspartate-based ubiquitous Mg(2+)-dependent phosphatasePhosphoglycolate hydrolase2-phosphoglycolate phosphataseP-glycolate phosphatasePhosphoglycollate phosphatasePGPase

Drugs targeting PGP (in Plasmodium) act as enzyme inhibitors, disrupting detoxification of phosphate esters, resulting in the accumulation of toxic metabolites and parasite death[5]. No established drugs for human PGP, so no clinical mechanism of action reported.