The Bacillus subtilis monothiol bacilliredoxin BrxC (YtxJ) and the Bdr (YpdA) disulfide reductase reduce S-bacillithiolated proteins

Abstract

The bacterial cytosol is generally a reducing environment with protein cysteine residues maintained in their thiol form. The low molecular weight thiol bacillithiol (BSH) serves as a general thiol reductant, analogous to glutathione, in a wide range of bacterial species. Proteins modified by disulfide bond formation with BSH ( S -bacillithiolation) are reduced by the action of bacilliredoxins, BrxA and BrxB. Here, the YtxJ protein is identified as a monothiol bacilliredoxin, renamed BrxC, and is implicated in BSH removal from oxidized cytosolic proteins, including the glyceraldehyde 3-phosphate dehydrogenases GapA and GapB. BrxC can also debacillithiolate the mixed disulfide form of the bacilliredoxin BrxB. Bdr is a thioredoxin reductase-like flavoprotein with bacillithiol-disulfide (BSSB) reductase activity. Here, Bdr is shown to additionally function as a bacilliredoxin reductase. Bdr and BrxB function cooperatively to debacillithiolate OhrR, a transcription factor regulated by S -bacillithiolation on its sole cysteine residue. Collectively, these results expand our understanding of the BSH redox network comprised of three bacilliredoxins and a BSSB reductase that serve to counter the widespread protein S -bacillithiolation that results from conditions of disulfide stress.

A sulfide-sensor and a sulfane sulfur-sensor collectively regulate sulfur-oxidation for feather degradation by Bacillus licheniformis

“…H 2 S is oxidized by SQR to sulfane sulfur, and sulfane sulfur is reduced by cellular thiols to form H 2 S and oxidized thiols 54 , 55 . B. licheniformis MW3 uses bacillithiol as its main intracellular low-molecular-weight thiol 56 , and it has similar chemical properties as GSH 57 . Hence, sulfide could be produced by oxidizing bacillithiol if sulfane sulfur accumulates in cells.…”

Atypical Bacilliredoxin AbxC Plays a Role in Responding to Oxidative Stress in Radiation-Resistant Bacterium Deinococcus radiodurans

“…This implies that AbxC participates in the H 2 O 2 -signaling pathway. Recently, it was found that B. subtilis BrxC (previously named YtxJ) can catalyze the de-bacillithiolation of several proteins [23]. The possibility of the dual function of AbxC as peroxidase in response to H 2 O 2 and as Brx in the de-bacillithiolation pathway cannot be ruled out because AbxC is the only homolog of Brx found in D. radiodurans.…”

“…BSH reacts directly with ROS, leading to the oxidation of BSH to BSSB [18]. Bacillus and Staphylococcus Bdr proteins have been recently shown to function as NADPH-dependent BSSB reductase [17,23,24]. To examine the BSSB reductase activity of DR_2623, a putative Bdr homolog, we analyzed the catalytic activity of purified DR_2623 (here designated DrBdr) in a BSH/NADPH-coupled assay in the presence of H 2 O 2 .…”

“…BrxC belonging to the Trx-like protein DUF2847 family is a monothiol Brx with the active site Cys located in a conserved TCPIS motif reminiscent of that found in monothiol Grx [12,22]. Recently, the B. subtilis BrxC protein has been shown to catalyze the de-bacillithiolation of BrxB and Bdr in vitro and GapDH in vivo [23].…”

Low-molecular-weight thiol transferases in redox regulation and antioxidant defence

“…The NADPH-dependent bacillithiol disulfide reductase (Bdr, also known as YpdA) reduces BSSB into two molecules of BSH [ 24 , [123] , [124] , [125] , [126] ]. A new bacilliredoxin, BrxC, which can reduce the BSH and BrxB mixed disulfide bond (BrxB-SB) and the BSH and Bdr mixed disulfide bond (BdrS-SB) was identified [ 127 ].…”