O-acetylserine sulfhydrylase (OASS)

O-acetylserine sulfhydrylase (OASS) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the final step of de novo L-cysteine biosynthesis in plants, bacteria, and certain protozoa [1, 3, 11]. It facilitates a beta-replacement reaction where the acetoxy group of O-acetylserine is substituted by sulfide or thiosulfate to produce cysteine [1, 12]. Because this biosynthetic pathway is absent in mammals—who must obtain cysteine through diet or conversion from methionine—OASS is considered a highly selective therapeutic target for antimicrobial and antiparasitic drug development [6, 7]. The enzyme typically exists as two major isoforms, OASS-A (CysK) and OASS-B (CysM), which exhibit distinct regulatory properties and expression patterns under aerobic or anaerobic conditions [3, 5]. Furthermore, OASS-A interacts with serine acetyltransferase to form the cysteine synthase complex, a key regulatory assembly in sulfur assimilation [4, 11]. Drug discovery efforts have yielded several investigational inhibitors, such as UPAR415, which act by competitively binding the active site to deplete sulfur-containing metabolites and weaken bacterial defense against oxidative stress [4, 5].

Other names

Cysteine synthaseO-acetylserine (thiol)-lyaseO-acetyl-L-serine sulfhydrylaseCysKCysMO3-acetyl-L-serine acetate-lyase

Competitive inhibition of the pyridoxal 5'-phosphate-dependent active site and disruption of the cysteine synthase bienzyme complex