Phosphoglycerate kinase

Phosphoglycerate kinase (EC 2.7.2.3) (PGK 1) is an enzyme that catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate (1,3-BPG) to ADP producing 3-phosphoglycerate (3-PG) and ATP :GlucoseHexokinaseGlucose 6-phosphateGlucose-6-phosphateisomeraseFructose 6-phosphatephosphofructokinase-1Fructose 1,6-bisphosphateFructose-bisphosphatealdolaseDihydroxyacetone phosphate+Glyceraldehyde 3-phosphateTriosephosphateisomerase2 × Glyceraldehyde 3-phosphateGlyceraldehyde-3-phosphatedehydrogenase2 × 1,3-BisphosphoglyceratePhosphoglycerate kinase2 × 3-PhosphoglyceratePhosphoglycerate mutase2 × 2-PhosphoglyceratePhosphopyruvatehydratase (Enolase)2 × PhosphoenolpyruvatePyruvate kinase2 × Pyruvate Phosphoglycerate kinase (EC 2.7.2.3) (PGK 1) is an enzyme that catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate (1,3-BPG) to ADP producing 3-phosphoglycerate (3-PG) and ATP : Like all kinases it is a transferase. PGK is a major enzyme used in glycolysis, in the first ATP-generating step of the glycolytic pathway. In gluconeogenesis, the reaction catalyzed by PGK proceeds in the opposite direction, generating ADP and 1,3-BPG. In humans, two isozymes of PGK have been so far identified, PGK1 and PGK2. The isozymes have 87-88% identical amino acid sequence identity and though they are structurally and functionally similar, they have different localizations: PGK2, encoded by an autosomal gene, is unique to meiotic and postmeiotic spermatogenic cells, while PGK1, encoded on the X-chromosome, is ubiquitously expressed in all cells. PGK is present in all living organisms as one of the two ATP-generating enzymes in glycolysis. In the gluconeogenic pathway, PGK catalyzes the reverse reaction. Under biochemical standard conditions, the glycolytic direction is favored. In the Calvin cycle in photosynthetic organisms, PGK catalyzes the phosphorylation of 3-PG, producing 1,3-BPG and ADP, as part of the reactions that regenerate ribulose-1,5-bisphosphate. PGK has been reported to exhibit thiol reductase activity on plasmin, leading to angiostatin formation, which inhibits angiogenesis and tumor growth. The enzyme was also shown to participate in DNA replication and repair in mammal cell nuclei. The human isozyme PGK2, which is only expressed during spermatogenesis, was shown to be essential for sperm function in mice. Click on genes, proteins and metabolites below to link to respective articles. PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a 415-residue monomer containing two nearly equal-sized domains that correspond to the N- and C-termini of the protein. 3-phosphoglycerate (3-PG) binds to the N-terminal, while the nucleotide substrates, MgATP or MgADP, bind to the C-terminal domain of the enzyme. This extended two-domain structure is associated with large-scale 'hinge-bending' conformational changes, similar to those found in hexokinase. The two domains of the protein are separated by a cleft and linked by two alpha-helices. At the core of each domain is a 6-stranded parallel beta-sheet surrounded by alpha helices. The two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded. Though the binding of either substrate triggers a conformational change, only through the binding of both substrates does domain closure occur, leading to the transfer of the phosphate group.