Phosphoglycolate phosphatase(EC 3.1.3.18; systematic name 2-phosphoglycolate phosphohydrolase), also commonly referred to as phosphoglycolate hydrolase, 2-phosphoglycolate phosphatase, P-glycolate phosphatase, and phosphoglycollate phosphatase, is an enzyme responsible for catalyzing the conversion of 2-phosphoglycolate into glycolate and phosphate:
2-phosphoglycolate + H2O = glycolate + phosphate First studied and purified within plants, phosphoglycolate phosphatase plays a major role in photorespiratory 2-phosphoglycolate metabolism, an essential pathway for photosynthesis in plants. The occurrence of photorespiration in plants, due to the lack of substrate specificity of rubisco, leads to the formation of 2-phosphoglycolate and 3-phosphoglycerate. 3-phosphogylcerate is the normal product of carboxylation and will enter the Calvin cycle. Phosphoglycolate, which is a potent inhibitor of phosphofructokinase and triosephosphate isomerase, must be quickly metabolized and transformed into a useful substrate, and phosphoglycolate phosphatase catalyzes the first step in the regeneration of 3-phosphoglycerate from 2-phosphoglycolate at the expense of energy in the form of ATP. Since the discovery of its activity in plants, it has been purified within human cells and implicated in 2,3-DPG regulation.
Structure The structural characterization of phosphoglycolate phosphatase from Thermoplasma acidophilum (PDB 1L6R, pictured) revealed the monomer of the dimeric enzyme (indicated by the light blue and green coloring) includes two distinct domains, a smaller cap domain and a larger core domain. While the topology of the large domain is conserved, there is structural variation of the smaller domain. The active site of the protein is a continuous tunnel through the monomer and is lined with acidic residues, a feature consistent with other acid phosphatases. In addition, electrostatic surface analysis indicates a relatively acidic surface.
Active site and The crystallization of phosphoglycolate phosphatase from Thermoplasma acidophilum revealed 5 active sites indicated by the blue spheres in the image. The key residues of the active site are aspartate, lysine, and serine.
Mechanism This enzyme belongs to the family of hydrolases, specifically those acting on phosphoric monoester bonds.
The hydrolysis of phosphoglycolate begins with the nucleophilic attack by an aspartate residue on the electrophilic phosphorus of the phosphoglycolate. The susceptibility of the bond between phosphate and glycolate is heightened by two key interactions. An interaction with the cofactor, Mg2+, helps polarize the phosphate-oxygen bond and therefore increases the electrophilicity of the phosphorus atom. The other interaction of the phosphate with serine and lysine residues further increases the electrophilicity of the phosphorus atom. In addition, the Mg2+ also orients the nucleophilic aspartate. The loss of the phosphate glycolate bond causes the nucleophilic aspartate to be phosphorylated, producing the enzyme intermediate, while glycolate is released from the active site. The interaction of the phosphorylated intermediate is stabilized by an interaction between the phosphate and a lysine residue. The Mg2+ located in the active site activates a water molecule to produce an hydroxide ion, which then hydrolyzes the phosphorylated aspartate and regenerates an active enzyme while releasing phosphate.
Function
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