Role of Histidine-152 in cofactor orientation in the PLP-dependent O-acetylserine sulfhydrylase reaction.

O-Acetylserine sulfhydrylase catalyzes the final step of the biosynthesis of l-cysteine, the replacement of the beta-acetoxy group of O-acetyl-l-serine (OAS) by a thiol. The 5'-phosphate of the PLP cofactor is very tightly bound to the enzyme; it accepts 8 hydrogen bonds from enzyme side chains and a pair of water molecules, and is in close proximity to a helix dipole. Histidine-152 (H152) is one of the residues that, via a water molecule, is responsible for positioning the 5'-phosphate.

Effect of mutation of lysine-120, located at the entry to the active site of O-acetylserine sulfhydrylase-A from Salmonella typhimurium.

O-Acetylserine sulfhydrylase catalyzes the final step of the biosynthesis of L-cysteine, the replacement of the beta-acetoxy group of O-acetyl-L-serine (OAS) by a thiol. The enzyme undergoes a conformational change to close the site upon formation of the external Schiff base (ESB) with OAS. Mutation of K120 to Q was predicted to destabilize the closed form of the ESB and decrease the rate.