O-acetylserine sulfhydrylase B (OASS-B)

O-acetylserine sulfhydrylase B (OASS-B), also known as CysM, is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the final step of de novo cysteine biosynthesis in various bacteria and plants [1, 5]. Unlike its isoform OASS-A (CysK), OASS-B is uniquely capable of utilizing thiosulfate as a sulfur source in addition to sulfide, which is particularly important under anaerobic or sulfur-limited conditions [2, 4, 18]. This enzyme plays a critical role in maintaining the cellular redox state and supporting the synthesis of essential sulfur-containing biomolecules like glutathione and iron-sulfur clusters [3, 13]. Because the reductive sulfate assimilation pathway is absent in mammals, OASS-B is a highly attractive target for the development of novel narrow-spectrum antibiotics and adjuvants to combat antimicrobial resistance [1, 5, 13]. Inhibition of OASS-B has been shown to increase bacterial susceptibility to existing antibiotics and impair survival within the host environment [3, 8, 13]. Current drug discovery efforts focus on small-molecule competitive inhibitors, such as cyclopropane-carboxylic acid derivatives, which aim to disrupt the enzyme's active site and deplete the bacterial cysteine pool [1, 6, 11].

Other names

CysMCysteine synthase BO-acetyl-L-serine sulfhydrylase BO-acetylserine (thiol)-lyase BS-sulfocysteine synthaseCysK2

Competitive inhibition of the active site