Gamma-glutamyl phosphate reductase (GPR), also known as glutamate-5-semialdehyde dehydrogenase, catalyses the second step of proline biosynthesis, the NADPH-dependent reversible reduction of gamma-glutamyl phosphate to glutamate-5-semialdehyde as shown below. L-glutamyl 5-phosphate + NADPH + H(+) = L-glutamate 5-semialdehyde + phosphate + NADP(+) In bacteria and yeast, GPR is a monofunctional protein, while in plants and mammals, it is part of a bifunctional enzyme that consists of two domains, an N-terminal glutamate 5-kinase domain (EC: 2.7.2.11) and a C-terminal GPR domain [PMID:11375165, PMID:8896266, PMID:1384052].

This entry represents the monofunctional gamma-glutamyl phosphate reductase found in bacteria and yeasts. Structural studies indicate that this protein is composed of three domains and belongs to the aldehyde dehydrogenase structural family [PMID:14705032]. The first two domains, the catalytic and cofactor binding domains respectively, both form a similar three layered alpha-beta-alpha fold, and are thought to close around the NADPH and gamma-glutamyl-phosphate ligands upon binding in order to orient a conserved cysteine residue for catalysis. The third domain is the oligomerisation domain which forms an antiparallel beta sheet. The biological oligomerisation state of the protein is not currently known, but like most members of the aldehyde dehydrogenase family it is expected to be either a dimer or a tetramer.