InterPro domain: IPR041744

This is the glutamate-5-kinase (G5K) domain of the bifunctional delta 1-pyrroline-5-carboxylate synthetase (P5CS), composed of an N-terminal G5K (ProB) and a C-terminal glutamyl 5- phosphate reductase (G5PR, ProA), the first and second enzyme catalyzing proline (and, in mammals, ornithine) biosynthesis. G5K transfers the terminal phosphoryl group of ATP to the gamma-carboxyl group of glutamate, and is subject to feedback allosteric inhibition by proline or ornithine. In plants, proline plays an important role as an osmoprotectant and, in mammals, ornithine biosynthesis is crucial for proper ammonia detoxification, since a G5K mutation has been shown to cause human hyperammonaemia [ 1 , 2 ].

1. Activation of glutamate by gamma-glutamate kinase: formation of gamma-cis-cycloglutamyl phosphate, an analog of gamma-glutamyl phosphate. J. Biol. Chem. 264, 11326-35
2. Molecular enzymology of mammalian Delta1-pyrroline-5-carboxylate synthase. Alternative splice donor utilization generates isoforms with different sensitivity to ornithine inhibition. J. Biol. Chem. 274, 6754-62