InterPro domain: IPR006236

Phosphoglycerate dehydrogenases (PGDH) have at least two different structural domains: the nucleotide binding and the substrate binding. There are three types of PGDH: type 3 enzymes are composed only of these two domains, type2 enzymes contain an extra C-terminal regulatory domain (ACT domain), type 1 enzymes contain both the regulatory domain and an extra allosteric domain [ 1 , 2 ]. This entry represents the type 1 enzyme. Interestingly, this type of PGDH is found in bacteria such as Mycobacterium, Bacillus subtilis, Corynebacterium, plants such as Arabidopsis, and higher order eukaryotes, including mammals. The PGDHs from E. coli and some lower eukaryotes, such as yeast and Neurospora, belong to the type2 PGDH and are not included in this entry [ 3 ].

PGDH catalyses an early step in the biosynthesis of L-serine by converting D-3-phosphoglyceric acid to hydroxypyruvic acid phosphate (HPAP), utilising NAD+ as a coenzyme [ 3 , 4 ]. Type 1 PGDH is mostly studied in M. tuberculosis. Both E.coli and M. tuberculosis PGDHs are very sensitive to inhibition by L-serine [ 4 ]. However, the mammalian enzymes are not inhibited by L-serine. The structural difference between human and M. tuberculosis PGDHs may explain the differential sensitivity to serine inhibition [ 4 ].

1. Contrasting catalytic and allosteric mechanisms for phosphoglycerate dehydrogenases. Arch. Biochem. Biophys. 519, 175-85
2. Crystal structure of Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase: extreme asymmetry in a tetramer of identical subunits. J. Biol. Chem. 280, 14892-9
3. Transient kinetic analysis of the interaction of L-serine with Escherichia coli D-3-phosphoglycerate dehydrogenase reveals the mechanism of V-type regulation and the order of effector binding. Biochemistry 48, 12242-51