PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a monomer containing two nearly equal-sized domains that correspond to the N- and C-termini of the protein (the last 15 C-terminal residues loop back into the N-terminal domain). 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 [PMID:10593256]. At the core of each domain is a 6-stranded parallel beta-sheet surrounded by alpha helices. Domain 1 has a parallel beta-sheet of six strands with an order of 342156, while domain 2 has a parallel beta-sheet of six strands with an order of 321456. Analysis of the reversible unfolding of yeast phosphoglycerate kinase leads to the conclusion that the two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded [PMID:2124145].

Phosphoglycerate kinase (PGK) deficiency is associated with haemolytic anaemia and mental disorders in man [PMID:6689547].