Table 1.

Examples of proteins containing the redox-sensing motif Cys-X-X-Cys. (*) The references given are for the protein from the strain listed. Sequence alignments demonstrate that highly homologous proteins are found across many different bacterial species.

	Name	Strain*	Function	Zn2+-binding
Enzymatic function	Hsp33	Escherichia coli	The redox-regulated heat shock protein Hsp33 is a dual stress sensor responding to peroxide stress and increased temperature. Stress-mediated conformational changes result in zinc release and activation of Hsp33 chaperone function leading to suppression of protein aggregation [18].	Yes
	Trx2	Escherichia coli	Trx2 reductase activity is controlled by a redox switch within two CXXC motifs involved in zinc binding. Release of the bound zinc ion results in a conformational change leading to the reductase activity [23].	Yes
	ResA	Bacillus subtilis	Substrate selection of the membrane-bound thiol-disulfide oxidoreductase ResA is regulated by conformational changes determined by CXXC reduction or oxidation [24].	No
	DsbA	Escherichia coli	DsbA is a periplasmic protein oxidant for disulfide formation of extracellular proteins belonging to the Dsb family [25].	No
	SbcC	Bacillus subtilis	SbcC is a DNA repair protein with exonuclease activity [27].	Yes
	Cytochrome c	Bacillus subtilis	The covalent coordination of heme to apo-cytochrome c requires a reduced CXXC motif within the heme-binding motif [28].	No
	AhpF/AhpC	Salmonella typhimurium	AhpC and flavoprotein AhpF catalyze the pyridine nucleotide-dependent reduction of hydroperoxide substrates. AhpC, the peroxide-reducing component, is a scavenger of hydrogen peroxide in bacteria, whereas the disulfide reductase protein AhpF regenerates AhpC [29].	No
	CopA	Thermotoga maritima	CopA, a copper transport ATPase, sustains important roles in homeostasis of heavy metals and delivery of copper to metalloenzymes [30].	No
	HypA	Escherichia coli	HypA is required for nickel insertion into the hydrogenase precursor proteins [31].	No
Transcriptional regulator	FurS	Streptomyces reticuli	Oxidation of the transcriptional repressor FurS leads to derepression of the transcription of the gene cpeB coding for a catalase peroxidase [6].	Yes
	CatR	Streptomyces coelicolor A3 (2)	During peroxide stress, the Fur-like regulator CatR activates transcription of catA coding for catalase A [21].	No
	WhiB3	Mycobacterium tuberculosis	WhiB3 DNA binding to control the expression of genes coding for polyketide synthases is reversibly regulated by a thiol-disulfide redox switch. Reduction of the apo-WhiB3 Cys thiols of the CXXC motif suppresses genes regulating the synthesis of complex lipids, whereas oxidation stimulates it [22].	No
	SoxR	Escherichia coli	SoxR senses superoxide stress through a CXXC-coordinated [2Fe-2S]-cluster that results in transcriptional activation of a superoxide response regulon [32].	No
	SurR	Pyrococcus furiosus (Archaea)	A redox switch regulates the transcriptional regulator SurR. Oxidation with S0 inhibits DNA binding by SurR, leading to repression of genes related to H2 production and activation of genes involved in S0 metabolism [33].	No
Regulatory element	Spx	Bacillus subtilis	Global oxidative stress regulator interacting with the α-subunit of RNA polymerase for transcriptional induction of genes involved in thiol homeostasis (mrsA-mrsB operon) [19].	No
	RsrA	Streptomyces coelicolor A3 (2)	Antisigma factor RsrA negatively regulates expression of the thioredoxin system in response to cytoplasmatic oxidative stress. Under reducing conditions, RsrA binds to σ R resulting in inhibition of transcription [20].	Yes
	RslA	Mycobacterium tuberculosis	Membrane-associated RslA oxidation results in the release of bound Zn2+ through disulfide bond formation within the CXXC motif. The resulting conformational change leads to decreased σ L binding. The released sigma factor regulates the expression of genes involved in cell-wall and polyketide synthesis [17].	Yes
	RshA	Mycobacterium tuberculosis	RshA is an antisigma factor of the central regulator SigH that responds to oxidative and heat stress; it functions as a negative regulator of the alternative sigma factor SigH activity under reducing conditions [26].	No