Insights into multifaceted activities of CysK for therapeutic interventions

Abstract

CysK (O-acetylserine sulfhydrylase) is a pyridoxal-5′ phosphate-dependent enzyme which catalyzes the second step of the de novo cysteine biosynthesis pathway by converting O-acetyl serine (OAS) into l-cysteine in the presence of sulfide. The first step of the cysteine biosynthesis involves formation of OAS from serine and acetyl CoA by CysE (serine acetyltransferase). Apart from role of CysK in cysteine biosynthesis, recent studies have revealed various additional roles of this enzyme in bacterial physiology. Other than the suggested regulatory role in cysteine production, other activities of CysK include involvement of CysK-in contact-dependent toxin activation in Gram-negative pathogens, as a transcriptional regulator of CymR by stabilizing the CymR-DNA interactions, in biofilm formation by providing cysteine and via another mechanism not yet understood, in ofloxacin and tellurite resistance as well as in cysteine desulfurization. Some of these activities involve binding of CysK to another cellular partner, where the complex is regulated by the availability of OAS and/or sulfide (H 2 S). The aim of this study is to present an overview of current knowledge of multiple functions performed by CysK and identifying structural features involved in alternate functions. Due to possible role in disease, promoting or inhibiting a "moonlighting" function of CysK could be a target for developing novel therapeutic interventions.

Tylosin Inhibits Streptococcus suis Biofilm Formation by Interacting With the O-acetylserine (thiol)-lyase B CysM

“…In Staphylococcus mutans, O-acetylserine sulfatase (CysK) overexpression increases cysteine synthesis, which in turn promotes biofilm formation (31). Furthermore, in vitro testing has showed that CysK gene deletion inhibits biofilm formation by reducing polysaccharide production (32). Thus, we also explored whether a similar phenomenon occurs in S. suis.…”

Exoproteome Analysis of Antagonistic Interactions between the Probiotic Bacteria Limosilactobacillus reuteri LR1 and Lacticaseibacillus rhamnosus F and Multidrug Resistant Strain of Klebsiella pneumonia

“…For L. reuteri LR1, the possible moonlighting function can be proposed for Cysteine synthase A (CysK) whose secretion can be associated with the presence of K. pneumoniae (ReKl and ReRhKl). CysK typically carries out the second step in the pathway of cysteine biosynthesis, synthesizing cysteine from sulfide (H 2 S) and O-acetyl-L-serine; however, it has been shown that in certain bacteria, including Lactobacillus casei, this enzyme can perform cysteine desulfurization leading to the formation of pyruvate, ammonia (NH 3 ) and H 2 S [47]. Recent investigations demonstrate that the presence of both NH 3 and H 2 S during cultivation significantly influenced bacterial physiology [48,49].…”

Molecular mechanism of selective substrate engagement and inhibitor disengagement of cysteine synthase

“…However, selective targeting remains a major challenge to drug discovery groups due to the paucity of information about details of complex formation and dissociation. Enzymes of cysteine biosynthesis pathway, including CS (CysK), have been considered as potential drug targets ( 36 , 37 , 38 , 39 , 40 ). Using structure-based in silico screening, multiple studies have identified several inhibitors against CS and its homologue, CysM ( 41 ).…”