Crystal structures of the reduced, sulfenic acid, and mixed disulfide forms of SarZ, a redox active global regulator in Staphylococcus aureus.
SarZ is a global transcriptional regulator that uses a single cysteine residue, Cys(13), to sense peroxide stress and control metabolic switching and virulence in Staphylococcus aureus. SarZ belongs to the single-cysteine class of OhrR-MgrA proteins that play key roles in oxidative resistance and virulence regulation in various bacteria. We present the crystal structures of the reduced form, sulfenic acid form, and mixed disulfide form of SarZ. Both the sulfenic acid and mixed disulfide forms are structurally characterized for the first time for this class of proteins. The Cys(13) sulfenic acid modification is stabilized through two hydrogen bonds with surrounding residues, and the overall DNA-binding conformation is retained. A further reaction of the Cys(13) sulfenic acid with an external thiol leads to formation of a mixed disulfide bond, which results in an allosteric change in the DNA-binding domains, disrupting DNA binding. Thus, the crystal structures of SarZ in three different states provide molecular level pictures delineating the mechanism by which this class of redox active regulators undergoes activation. These structures help to understand redox-mediated virulence regulation in S. aureus and activation of the MarR family proteins in general.
Poor
Catherine B
CB
Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
Chen
Peng R
PR
Duguid
Erica
E
Rice
Phoebe A
PA
He
Chuan
C
D000595:Amino Acid Sequence; D003460:Crystallization; D004220:Disulfides / Q000737:chemistry*; D005809:Genes, Regulator; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013434:Sulfenic Acids / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D004220:Disulfides; C534537:SarZ protein, Staphylococcus aureus; D013434:Sulfenic Acids; D014157:Transcription Factors