PDBsum entry 2bv6

Transcriptional regulator

PDB id: 2bv6

Contents

Protein chain

137 a.a. *

Ligands

SO4

Waters ×9

* Residue conservation analysis

PDB id:

2bv6

Name:

Transcriptional regulator

Title:

Crystal structure of mgra, a global regulator and major virulence determinant in staphylococcus aureus

Structure:

Hth-type transcriptional regulator mgra. Chain: a. Fragment: residues 5-142. Synonym: mgra. Engineered: yes

Source:

Staphylococcus aureus. Organism_taxid: 1280. Strain: newman. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.80Å R-factor: 0.250 R-free: 0.292

Authors:

P.R.Chen,T.Bae,W.A.Williams,E.M.Duguid,P.A.Rice,O.Schneewind,C.He

Key ref:

P.R.Chen et al. (2006). An oxidation-sensing mechanism is used by the global regulator MgrA in Staphylococcus aureus. Nat Chem Biol, 2, 591-595. PubMed id: 16980961 DOI: 10.1038/nchembio820

Date:

22-Jun-05 Release date: 20-Sep-06

Protein chain

P0C1S0  (MGRA_STAAU) -  HTH-type transcriptional regulator MgrA from Staphylococcus aureus

Seq: 147 a.a.

Struc: 137 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nchembio820

Nat Chem Biol 2:591-595 (2006)

PubMed id: 16980961

An oxidation-sensing mechanism is used by the global regulator MgrA in Staphylococcus aureus.

P.R.Chen, T.Bae, W.A.Williams, E.M.Duguid, P.A.Rice, O.Schneewind, C.He.

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.

Selected figure(s)

Figure 2.
(a) Ribbon representation of the MgrA dimer with one subunit colored blue and the dyadic mate colored green. The N and C termini and secondary structural elements of one monomer are labeled ( , -helices; , -sheets; W1, the wing region). Numbering is according to MgrA primary sequence (Supplementary Fig. 4). Potential DNA-interacting basic residues on the DNA binding domain are shown together with one ordered sulfate anion per monomer.

Figure 4.
(a,b) The change in susceptibility of S. aureus strains to ciprofloxacin (CIP) and vancomycin (VCM) under oxidative stress. The antibiotic resistance levels were tested in the absence (-H[2]O[2]) or presence (+H[2]O[2]) of 100 M H[2]O[2] by a plate sensitivity assay (a) and were also determined in the absence (-PQ) or presence (+PQ) of 25 M paraquat by a 96-well plate sensitivity assay (b). Under normal growth conditions (control) the five strains did not show noticeable differences. The wild-type strain and the mgrA mutant strain complemented with pYJ335-His-mgrA showed higher susceptibility toward CIP and VCM. Under oxidation conditions both strains showed increased resistance, comparable to that of the mgrA mutant strain, toward these antibiotics. In control experiments, the pYJ335-His-mgrAC12S–containing mutant strain did not change its susceptibility toward CIP and VCM under normal versus oxidative conditions. (c) Induction of norA, a gene regulated by mgrA, by oxidative stress. -Galactosidase activity of strains containing the norA-lacZ reporter fusion was determined in the wild-type (Newman) and mgrA mutant ( N 3040) strains and expressed in MUG units (MUG, 4-methylumbelliferyl- -D-galactopyranoside; 1 MUG unit = 1 pmol of MUG cleaved by -galactosidase per min per OD[600]). Empty bars are untreated cultures. Results are mean s.d. from three independent experiments performed in duplicate.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Chem Biol (2006, 2, 591-595) copyright 2006.

Figures were selected by an automated process.