The multifaceted pyridoxal 5′-phosphate-dependent O-acetylserine sulfhydrylase

Cysteine is the final product of the reductive sulfate assimilation pathway in bacteria and plants and serves as the precursor for all sulfur-containing biological compounds, such as methionine, S-adenosyl methionine, iron–sulfur clusters and glutathione. Moreover, in several microorganisms cysteine plays a role as a reducing agent, eventually counteracting host oxidative defense strategies. Cysteine is synthesized by the PLP-dependent O-acetylserine sulfhydrylase, a dimeric enzyme belonging to the fold type II, catalyzing a beta-replacement reaction. In this review, the spectroscopic properties, catalytic mechanism, three-dimensional structure, conformational changes accompanying catalysis, determinants of enzyme stability, role of selected amino acids in catalysis, and the regulation of enzyme activity by ligands and interaction with serine acetyltransferase, the preceding enzyme in the biosynthetic pathway, are described. Given the key biological role played by O-acetylserine sulfhydrylase in bacteria, inhibitors with potential antibiotic activity have been developed. This article is part of a Special Issue entitled: Pyridoxal Phospate Enzymology. [Display omitted] ► In bacteria and plants cysteine is the key amino acid of sulfur assimilation. ► The PLP-dependent O-acetylserine sulfhydrylase catalyzes cysteine synthesis. ► O-acetylserine sulfhydrylase catalysis is accompanied by an open–closed transition. ► Absorption and fluorescence changes allowed to unveil the catalytic mechanism. ► Enzyme mechanism has been determined by steady- and presteady-state kinetics. ► Enzyme inhibitors with potential antibiotic activity have been developed.