2BV6

Crystal structure of MgrA, a global regulator and major virulence determinant in Staphylococcus aureus

Summary for 2BV6

• Entry DOI: 10.2210/pdb2bv6/pdb
• Descriptor: HTH-TYPE TRANSCRIPTIONAL REGULATOR MGRA, SULFATE ION (3 entities in total)
• Functional Keywords: transcriptional regulator, multidrug resistance regulator, virulence determinant, transcriptional factors
• Biological source: STAPHYLOCOCCUS AUREUS
• Cellular location: Cytoplasm (Probable): Q7X448
• Total number of polymer chains: 1
• Total formula weight: 16629.57

Authors

Chen, P.R.,Bae, T.,Williams, W.A.,Duguid, E.M.,Rice, P.A.,Schneewind, O.,He, C. (deposition date: 2005-06-22, release date: 2006-09-20, Last modification date: 2011-07-13)

Primary citation

Chen, P.R.,Bae, T.,Williams, W.A.,Duguid, E.M.,Rice, P.A.,Schneewind, O.,He, C.
An Oxidation-Sensing Mechanism is Used by the Global Regulator Mgra in Staphylococcus Aureus.
Nat.Chem.Biol., 2:591-, 2006

PubMed Abstract: Staphylococcus aureus is a human pathogen responsible for most wound and hospital-acquired infections. The protein MgrA is both an important virulence determinant during infection and a regulator of antibiotic resistance in S. aureus. The crystal structure of the MgrA homodimer, solved at 2.86 A, indicates the presence of a unique cysteine residue located at the interface of the protein dimer. We discovered that this cysteine residue can be oxidized by various reactive oxygen species, such as hydrogen peroxide and organic hydroperoxide. Cysteine oxidation leads to dissociation of MgrA from DNA and initiation of signaling pathways that turn on antibiotic resistance in S. aureus. The oxidation-sensing mechanism is typically used by bacteria to counter challenges of reactive oxygen and nitrogen species. Our study reveals that in S. aureus, MgrA adopts a similar mechanism but uses it to globally regulate different defensive pathways.

PubMed: 16980961
DOI: 10.1038/NCHEMBIO820

Experimental method

X-RAY DIFFRACTION (2.8 Å)