O-acetylserine sulfhydrylase A (OASS-A)

O-acetylserine sulfhydrylase A (OASS-A), also known as CysK, is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the final step of L-cysteine biosynthesis in bacteria and plants [1, 6]. It facilitates the β-replacement of the acetoxy group of O-acetylserine with bisulfide to produce cysteine [9, 19]. This enzyme is a key component of the cysteine synthase complex, where it interacts with serine acetyltransferase (SAT) [7, 14]. Because the reductive sulfate assimilation pathway is absent in mammals, OASS-A is a promising target for the development of novel antibacterial agents and adjuvants to combat antimicrobial resistance [1, 16]. Inhibitors of OASS-A, such as UPAR415 and various fluoroalanine derivatives, aim to disrupt bacterial sulfur metabolism, thereby increasing sensitivity to oxidative stress and conventional antibiotics [4, 15]. Research indicates that targeting OASS-A can enhance the efficacy of existing drugs like colistin against Gram-negative pathogens [4, 5].

Other names

Cysteine synthase AO-acetylserine (thiol)-lyase ACSase AOAS-TL ACysKSulfide-dependent cysteine synthase

Competitive inhibition of O-acetylserine sulfhydrylase activity and disruption of the cysteine synthase complex [4, 7, 16].