3T8R: Crystal Structure Of Staphylococcus Aureus Cymr

As a human pathogen, Staphylococcus aureus must cope with oxidative stress generated by the human immune system. Here, we report that CymR utilizes its sole Cys-25 to sense oxidative stress. Oxidation followed by thiolation of this cysteine residue leads to dissociation of CymR from its cognate promoter DNA. In contrast, the DNA binding of the CymRC25S mutant was insensitive to oxidation and thiolation, suggesting that CymR senses oxidative stress through oxidation of its sole cysteine to form a mixed disulfide with low molecular weight thiols. The determined crystal structures of the reduced and oxidized forms of CymR revealed that Cys-25 is oxidized to Cys-25-SOH in the presence of H(2)O(2). Deletion of cymR reduced the resistance of S. aureus to oxidative stresses, and the resistance was restored by expressing a C25S mutant copy of cymR. In a C25S substitution mutant, the expression of two genes, tcyP and mccB, was constitutively repressed and did not respond to hydrogen peroxide stress, whereas the expression of the genes were highly induced under oxidative stress in a wild-type strain, indicating the critical role of Cys-25 in redox signaling in vivo. Thus, CymR is another master regulator that senses oxidative stress and connects stress responses to virulence regulation in S. aureus.
PDB ID: 3T8RDownload
MMDB ID: 99655
PDB Deposition Date: 2011/8/1
Updated in MMDB: 2012/07
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3T8R: dimeric; determined by author and by software (PISA)
Molecular Components in 3T8R
Label Count Molecule
Proteins (2 molecules)
Staphylococcus Aureus Cymr
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB