OxyR a sensor of peroxide stressDespitetherebeinglittledoubtthatOxyRusesoneormoreof itssixcysteinethiolstodirectlysense oxidative stress,the precise nature of thethiolmodifications andtheirconsequences for OxyR activity are the subject of ongoing controversy.Storz laboratory supported the role of just one, Cys199,in the hydrogen peroxidemediatedactivationofOxyR,possiblythroughtheformationofsulphenicacid(SOH)StamlerlaboratoryshowedthatOxyRcouldalsobeactivatedbyS-nitrosylationwhentreated with S-nitrosothiols (SNOs),thereby supporting the roleof the same singlecysteineinOxyRactivation.Storzsuggestedaroleforanothercysteines,Cys2o8,followingthedetectioninoxidizedOxyRofanintramoleculardisulphidebondbetweenCys199andCys208Stamler'sgrouprecentlycametotheconclusionthatCys2o8mightnothavearoleinOxyR activation15.Instead, theypresented evidencethatOxyRis modified byperoxidestresstoCys199-SOH;bynitrosativestresstoCys199-SNO;orbydisulphide stresstoforma mixed disulphide withglutathione(Cys199-S-SG)
OxyR — a sensor of peroxide stress • Despite there being little doubt that OxyR uses one or more of its six cysteine thiols to directly sense oxidative stress, the precise nature of the thiol modifications and their consequences for OxyR activity are the subject of ongoing controversy. • Storz laboratory supported the role of just one, Cys199, in the hydrogen peroxidemediated activation of OxyR, possibly through the formation of sulphenic acid (SOH). Stamler laboratory showed that OxyR could also be activated by S-nitrosylation when treated with S-nitrosothiols (SNOs), thereby supporting the role of the same single cysteine in OxyR activation. • Storz suggested a role for another cysteines, Cys208, following the detection in oxidized OxyR of an intramolecular disulphide bond between Cys199 and Cys208. • Stamler’s group recently came to the conclusion that Cys208 might not have a role in OxyR activation15. Instead, they presented evidence that OxyR is modified by peroxide stress to Cys199-SOH; by nitrosative stress to Cys199-SNO; or by disulphide stress to form a mixed disulphide with glutathione(Cys199-S-SG)
oR-RsrA a sensor of disulphide stressboR-RsrARsrADisulphideTrxAstressSHORTrXAZn2+regukonSHCoreRNAPSRsrA
σR-RsrA — a sensor of disulphide stress