Three-dimensional structure of O-acetylserine sulfhydrylase from Salmonella typhimurium

Abstract

The last step in cysteine biosynthesis in enteric bacteria is catalyzed by the pyridoxal 5′-phosphate-dependent enzyme O-acetylserine sulfhydrylase. Here we report the crystal structure at 2.2 Å resolution of the A-isozyme of O-acetylserine sulfhydrylase isolated from Salmonella typhimurium. O-acetylserine sulfhydrylase shares the same fold with tryptophan synthase-β from Salmonella typhimurium but the sequence identity level is below 20%. There are some major structural differences: the loops providing the interface to the α-subunit in tryptophan synthase-β and two surface helices of tryptophan synthase-β are missing in O-acetylserine sulfhydrylase. The hydrophobic channel for indole transport from the α to the β active site of tryptophan synthase-β is, not unexpectedly, also absent in O-acetylserine sulfhydrylase. The dimer interface, on the other hand, is more or less conserved in the two enzymes. The active site cleft of O-acetylserine sulfhydrylase is wider and therefore more exposed to the solvent. A possible binding site for the substrate O-acetylserine is discussed.