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Structural and functional characterization of ScsC, a periplasmic thioredoxin-like protein from Salmonella enterica serovar Typhimurium.

ABSTRACT: AIMS:The prototypical protein disulfide bond (Dsb) formation and protein refolding pathways in the bacterial periplasm involving Dsb proteins have been most comprehensively defined in Escherichia coli. However, genomic analysis has revealed several distinct Dsb-like systems in bacteria, including the pathogen Salmonella enterica serovar Typhimurium. This includes the scsABCD locus, which encodes a system that has been shown via genetic analysis to confer copper tolerance, but whose biochemical properties at the protein level are not defined. The aim of this study was to provide functional insights into the soluble ScsC protein through structural, biochemical, and genetic analyses. RESULTS:Here we describe the structural and biochemical characterization of ScsC, the soluble DsbA-like component of this system. Our crystal structure of ScsC reveals a similar overall fold to DsbA, although the topology of ?-sheets and ?-helices in the thioredoxin domains differ. The midpoint reduction potential of the CXXC active site in ScsC was determined to be -132 mV versus normal hydrogen electrode. The reactive site cysteine has a low pKa, typical of the nucleophilic cysteines found in DsbA-like proteins. Deletion of scsC from S. Typhimurium elicits sensitivity to copper (II) ions, suggesting a potential involvement for ScsC in disulfide folding under conditions of copper stress. INNOVATION AND CONCLUSION:ScsC is a novel disulfide oxidoreductase involved in protection against copper ion toxicity.

SUBMITTER: Shepherd M

PROVIDER: S-EPMC3797457 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Structural and functional characterization of ScsC, a periplasmic thioredoxin-like protein from Salmonella enterica serovar Typhimurium.

Shepherd Mark M Heras Begoña B Achard Maud E S ME King Gordon J GJ Argente M Pilar MP Kurth Fabian F Taylor Samantha L SL Howard Mark J MJ King Nathan P NP Schembri Mark A MA McEwan Alastair G AG

Antioxidants & redox signaling 20130809 13

<h4>Aims</h4>The prototypical protein disulfide bond (Dsb) formation and protein refolding pathways in the bacterial periplasm involving Dsb proteins have been most comprehensively defined in Escherichia coli. However, genomic analysis has revealed several distinct Dsb-like systems in bacteria, including the pathogen Salmonella enterica serovar Typhimurium. This includes the scsABCD locus, which encodes a system that has been shown via genetic analysis to confer copper tolerance, but whose bioch ...[more]

PMID: 23642141

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Dataset Information

Structural and functional characterization of ScsC, a periplasmic thioredoxin-like protein from Salmonella enterica serovar Typhimurium.

Publications

Structural and functional characterization of ScsC, a periplasmic thioredoxin-like protein from Salmonella enterica serovar Typhimurium.

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