3-DIMENSIONAL STRUCTURE OF O-ACETYLSERINE SULFHYDRYLASE FROM SALMONELLA-TYPHIMURIUM

The last step in cysteine biosynthesis in enteric bacteria is catalyze d by the pyridoxal 5'-phosphate-dependent enzyme O-acetylserine sulfhy drylase. Here we report the crystal structure at 2.2 Angstrom resoluti on of the A-isozyme of O-acetylserine sulfhydrylase isolated from Salm onella typhimurium. O-acetylserine sulfhydrylase shares the same fold with tryptophan synthase-beta from Salmonella typhimurium but the sequ ence identity level is below 20%. There are some major structural diff erences: the loops providing the interface to the alpha-subunit in try ptophan synthase-beta and two surface helices of tryptophan synthase-b eta are missing in O-acetylserine sulfhydrylase. The hydrophobic chann el for indole transport from the alpha to the beta active site of tryp tophan synthase-beta is, not unexpectedly, also absent in O-acetylseri ne sulfhydrylase. The dimer interface, on the other hand, is more or l ess conserved in the two enzymes. The active site cleft of O-acetylser ine sulfhydrylase is wider and therefore more exposed to the solvent. A possible binding site for the substrate O-acetylserine is discussed. (C) 1998 Academic Press.