Pyridoxal 5'-phosphate-binding protein involved in the homeostasis of vitamin B₆ and amino acids

Abstract

The YggS/PROSC(COG0325) protein is a highly conserved pyridoxal 5'-phosphate (PLP)-binding protein that plays an important role in the homeostasis of vitamin B₆ and amino acids. The deletion or mutation of this protein causes a wide variety of pleiotropic effects in many organisms and vitamin B₆-dependent epilepsy in animals including humans. In E. coli, the mutation of this protein (yggS mutation) caused diverse phenotypes including perturbation of Thr/Ile/Val metabolism, a decrease of CoA levels, homoserine sensitivity, pyridoxine sensitivity, and/or synthetic lethality with glyA encoding serine hydroxymethyltransferase. Little was known about the causes, mechanisms, and consequences of the diverse phenotypes observed in the deficiency of the YggS/PROSC protein. We have found that the mutation of this protein induces the accumulation of pyridoxine 5'-phosphate (PNP) in various organisms and have provided evidence that many of the phenotypes observed in the yggS-deficient E. coli are caused by the elevated PNP level in the cells.