PDBsum entry: 3hsr

Transcription regulator

PDB id: 3hsr

Contents

Protein chains

130 a.a. *

Ligands

BT6 ×3

ACT ×4

GOL ×5

Waters ×189

* Residue conservation analysis

PDB id:

3hsr

Name:

Transcription regulator

Title:

Crystal structure of staphylococcus aureus protein sarz in m disulfide form

Structure:

Hth-type transcriptional regulator sarz. Chain: a, b, c, d. Fragment: unp residues 7-142. Engineered: yes

Source:

Staphylococcus aureus subsp. Aureus. Organism_taxid: 426430. Strain: newman. Gene: nwmn_2286. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.199 R-free: 0.247

Authors:

C.B.Poor,E.Duguid,P.A.Rice,C.He

Key ref:

C.B.Poor et al. (2009). Crystal structures of the reduced, sulfenic acid, and mixed disulfide forms of SarZ, a redox active global regulator in Staphylococcus aureus. J Biol Chem, 284, 23517-23524. PubMed id: 19586910 DOI: 10.1074/jbc.M109.015826

Date:

10-Jun-09 Release date: 07-Jul-09

Protein chains

A6QJM6  (A6QJM6_STAAE) -  MarR family regulatory protein

Seq: 148 a.a.

Struc: 130 a.a.*

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

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: transcription, DNA-dependent (2 terms)
• Biochemical function: DNA binding (2 terms)

DOI no: 10.1074/jbc.M109.015826

J Biol Chem 284:23517-23524 (2009)

PubMed id: 19586910

Crystal structures of the reduced, sulfenic acid, and mixed disulfide forms of SarZ, a redox active global regulator in Staphylococcus aureus.

C.B.Poor, P.R.Chen, E.Duguid, P.A.Rice, C.He.

ABSTRACT

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.

Selected figure(s)

Figure 4.
Reactive Cys^13 pocket.A, reduced Cys (SH). B, sulfenic acid Cys (SOH). Atoms are colored gray (carbon), red (oxygen), and yellow (sulfur). Water molecules are labeled W1 or W2 and shown as red spheres. Hydrogen bonds are shown as black dashed lines. A, Ser^113′ to Tyr^41′ 2.8 Å; Ser^113′ to Tyr^27′ 2.9 Å; Cys^13 to Tyr^27′ 3.3 Å; Cys^13 to W1 3.9 Å; W1 to Tyr^38′ 2.5 Å. B, Ser^113′ to Tyr^41′ 3.5 Å; Ser^113′ to Tyr^27′ 2.7 Å; Cys^13-SOH Oδ to Tyr^27′ 3.0 Å; Cys^13-SOH Oδ to W1 2.7 Å; W1 to Tyr^38′ 2.6 Å; W2 to Cys^13-SOH Sγ 3.7 Å.

Figure 6.
Cys^13 pocket in SarZ-BT.A and B, BT-modified Cys^13 of monomer C (A) and D (B). Atoms are colored gray (carbon), red (oxygen), and yellow (sulfur). Hydrogen bonds are shown as black dashed lines. A, Ser^113′ to Tyr^41′ 3.8 Å; Ser^113′ to Tyr^27′ 2.6 Å; Cys^13-BT Sγ to Tyr^38′ 3.3 Å. B, Ser^113′ to Tyr^41′ 2.9 Å; Ser^113′ to Tyr^27′ 2.5 Å. C, overlay of SarZ-SH (blue), SarZ-SOH (green), and SarZ-BT (red) showing the steric clash between Cys-BT and Phe^117′ from either SarZ-SH or SarZ-SOH. In the SarZ-BT structure, Phe^117′ is flipped away from the modification.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 23517-23524) copyright 2009.

Figures were selected by an automated process.