Disease relevance of PGA

• Ribulose 1,5-bisphosphate carboxylase from Rhodospirillum rubrum requires CO2 and Mg2+ for activation of both CO2, both the carboxylase and oxygenase activities are stimulated by 6-phoshpo-D-gluconate, fructose 1,6-bisphosphate, 2-phosphoglycolate, 3-phosphoglycerate, NADPH, and fructose 6-phosphate [1].
• The occurrence of a photorespiratory 2-phosphoglycolate metabolism in cyanobacteria is not clear [2].
• Role of 2-phosphoglycolate phosphatase of Escherichia coli in metabolism of the 2-phosphoglycolate formed in DNA repair [3].
• The structure of the thermostable triosephosphate isomerase (TIM) from Bacillus stearothermophilus complexed with the competitive inhibitor 2-phosphoglycolate was determined by X-ray crystallography to a resolution of 2.8 A [4].

High impact information on PGA

• Enzymatic assays on TA0175 revealed that this enzyme catalyzed the dephosphorylation of phosphoglycolate in vitro with similar kinetic properties seen for eukaryotic phosphoglycolate phosphatase [5].
• Crystal structure of triosephosphate isomerase complexed with 2-phosphoglycolate at 0.83-A resolution [6].
• Fractionated human whole-cell extracts contained an activity, which in the presence of EDTA, catalyzed removal of glycolate from phosphoglycolate at a single-stranded 3' terminus to leave a 3'-phosphate, reminiscent of the human tyrosyl-DNA phosphodiesterase hTdp1 [7].
• Consistent with these observations, treatment of neutrophils with phosphoglycolic acid, a competitive PGAM-B inhibitor, increases upstream intermediates, thereby amplifying the respiratory burst [8].
• When a plasmid containing a double strand break with a 3'-phosphoglycolate on a 3-base 3' overhang was incubated in human cell extracts, phosphoglycolate processing proceeded rapidly for the first few minutes but then slowed dramatically, suggesting that the single-stranded overhangs gradually became sequestered and inaccessible to hTdp1 [7].

Chemical compound and disease context of PGA

• The plant-like c2 glycolate cycle and the bacterial-like glycerate pathway cooperate in phosphoglycolate metabolism in cyanobacteria [2].
• These results suggested that cyanobacteria metabolize phosphoglycolate by the cooperative action of the C2 cycle and the glycerate pathway [2].

Biological context of PGA

• In summary, monophosphoglycerates and 2-phosphoglycolate have partially distinct binding sites in human BPGM [9].
• Mechanism of phosphoglycolate phosphatase. Studies of hydrolysis and transphosphorylation, substrate analogs, and sulfhydryl inhibition [10].
• To study the route and importance of 2-phosphoglycolate metabolism, the identified genes were systematically inactivated by mutagenesis [2].
• We showed that this housekeeping enzyme is involved in the dissimilation of the intracellular 2-phosphoglycolate formed in the DNA repair of 3'-phosphoglycolate ends [3].
• Pyruvate kinase from rabbit muscle catalyzes an ATP-dependent phosphorylation of glycolate to yield 2-phosphoglycolate (F. J. Kayne (1974) Biochem. Biophys. Res. Commun. 59, 8-13) [11].

Anatomical context of PGA

• Mechanism of activation by anions of phosphoglycolate phosphatases from spinach and human red blood cells [12].
• Human HeLa cell enzymes that remove phosphoglycolate 3'-end groups from DNA [13].
• Enzymes with phosphoglycolate phosphatase activity in chicken skeletal muscle and liver [14].
• In the immobilized cells, the photorespiratory enzyme, phosphoglycolate phosphatase, was 75% higher than in freely suspended cells [15].

Associations of PGA with other chemical compounds

• Phosphoglycolate phosphatase (EC 3.1.3.18) was purified 1500-fold from field-grown tobacco leaves by acetone fractionation, DEAE-cellulose and molecular sieve chromatography, and preparative polyacrylamide gel electrophoresis [16].
• Although no exchange of D-[14C]glycerate into phospho-D-glycerate can be detected, the enzyme catalyzes the transfer of the phosphoryl group from "unnatural" donors such as 2-phosphoglycolate, to the "natural" acceptor, D-glycerate [17].
• TIM and its complexes with the reactive intermediate analogs, phosphoglycolic acid (PGA) and phosphoglycolohydroxamic acid (PGH), were studied by 1H NMR at 600 MHz and at low temperature (-4.8 degrees C) [18].
• Surprisingly, spectra of TIM ligated with a substrate analog, glycerol 3-phosphate (G3P), or with a tight-binding transition-state analog, phosphoglycolate (PGA), show that the loop moves with a rate similar to the rate in the empty enzyme and also has a similar population ratio for the two conformers [19].
• Cell-free extract, prepared from A549 lung carcinoma cells by sonication or treatment with toluene, efficiently removed the phosphoglycolate and unknown lesions, but was less reactive towards thymine glycols [20].

Gene context of PGA

• HAP1 was found to recognize the strand break, and catalyze the release of the 3'-phosphoglycolate as free phosphoglycolic acid [21].
• Similarly, the 27 kDa protein has 2-phosphoglycolate phosphatase activity (similar to CbbZ), and we name the gene gph [22].
• The binding of the transition-state analogue 2-phosphoglycolate to triosephosphate isomerase from yeast has been investigated crystallographically [23].
• Phosphoglycolate (PG) is a competitive inhibitor of enolase [24].
• The crystal structure of recombinant human triosephosphate isomerase (hTIM) has been determined complexed with the transition-state analogue 2-phosphoglycolate at a resolution of 2.8 A [25].

Analytical, diagnostic and therapeutic context of PGA

• Vectors with blunt or cohesive 3'-phosphoglycolate ends yielded single repair products corresponding to simple phosphoglycolate removal followed by ligation, while a vector with mismatched ends was also rejoined but yielded a mixture of products [26].
• BPGM variants were constructed by site-directed mutagenesis of three amino acid residues in the active site to identify residues specifically involved in the binding of the monophosphoglycerates and 2-phosphoglycolate [9].
• A combination of primary kinetic isotope effect measurements, isothermal calorimetric measurements, and (31)P NMR spectroscopic titration with the inhibitor 2-phosphoglycolate revealed that the mutants have a different ligand-binding mode than that of the wild-type enzyme [27].
• Phosphoglycolate (P-glycolate) phosphatase was purified 223-fold from spinach leaves by (NH4)2SO4 fractionation, DEAE-cellulose chromatography, and Sephadex G-200 chromatography [28].
• The structure was solved by the molecular replacement method, first at 2.8 A resolution with a crystal grown by the technique of hanging-drop crystallization from a mother liquor containing the transition-state analogue 2-phosphoglycolate (2PG) [29].

References