PDBsum entry: 3bpv

Transcription regulator

PDB id: 3bpv

Contents

Protein chain

137 a.a. *

Waters ×150

* Residue conservation analysis

PDB id:

3bpv

Name:

Transcription regulator

Title:

Crystal structure of marr

Structure:

Transcriptional regulator. Chain: a. Engineered: yes

Source:

Methanobacterium thermoautotrophicum. Gene: mth313,mth_313. Expressed in: escherichia coli.

Resolution:

1.40Å R-factor: 0.243 R-free: 0.264

Authors:

V.Saridakis,D.Shahinas,X.Xu,D.Christendat

Key ref:

V.Saridakis et al. (2008). Structural insight on the mechanism of regulation of the MarR family of proteins: high-resolution crystal structure of a transcriptional repressor from Methanobacterium thermoautotrophicum. J Mol Biol, 377, 655-667. PubMed id: 18272181 DOI: 10.1016/j.jmb.2008.01.001

Date:

19-Dec-07 Release date: 20-May-08

Protein chain

O26413  (O26413_METTH) -  Transcriptional regulator

Seq: 146 a.a.

Struc: 137 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: regulation of transcription (3 terms)
• Biochemical function: DNA binding (2 terms)

DOI no: 10.1016/j.jmb.2008.01.001

J Mol Biol 377:655-667 (2008)

PubMed id: 18272181

Structural insight on the mechanism of regulation of the MarR family of proteins: high-resolution crystal structure of a transcriptional repressor from Methanobacterium thermoautotrophicum.

V.Saridakis, D.Shahinas, X.Xu, D.Christendat.

ABSTRACT

Transcriptional regulators belonging to the MarR family are characterized by a winged-helix DNA binding domain. These transcriptional regulators regulate the efflux and influx of phenolic agents in bacteria and archaea. In Escherichia coli, MarR regulates the multiple antibiotic resistance operon and its inactivation produces a multiple antibiotic resistance phenotype. In some organisms, active efflux of drug compounds will produce a drug resistance phenotype, whereas in other organisms, active influx of chlorinated hydrocarbons results in their rapid degradation. Although proteins in the MarR family are regulators of important biological processes, their mechanism of action is not well understood and structural information about how phenolic agents regulate the activity of these proteins is lacking. This article presents the three-dimensional structure of a protein of the MarR family, MTH313, in its apo form and in complex with salicylate, a known inactivator. A comparison of these two structures indicates that the mechanism of regulation involves a large conformational change in the DNA binding lobe. Electrophoretic mobility shift assay and biophysical analyses further suggest that salicylate inactivates MTH313 and prevents it from binding to its promoter region.

Selected figure(s)

Figure 2.
Fig. 2. Comparison of the top DALI structural homologues at the helix–turn–helix motif reveals conservation of the ligand binding pocket in three-dimensional space. (a) Structure-based alignment of the top DALI structural homologues. (b) The identified salicylate binding site of M. thermoautotrophicum consists mainly of basic and hydrophobic residues. (c) E. faecalis SlyA (PDB ID: 1LJ9) is the closest structural homologue to MTH313. The binding site contains similar composition of hydrophobic and basic residues. (d) In B. subtilis OhrR (PDB ID: 1Z91), the redox cysteine, residue 15, is identified in the binding pocket (substituted to Ser15 in the coordinate file). (e) The identified binding site in E. coli MarR (1JGS). (f) The identified binding site for EmrR from S. tokodaii (2GXG). The identified binding site contains a high proportion of polar and charged residues.

Figure 3.
Fig. 3. (a) Electrostatic surface representation of MTH313 in the apo and in complex with salicylate. The arrow is pointing at the first binding site. The identified binding pocket consists of a high proportion of basic residues, which may indicate its potential to bind different ligands. (b) Electrostatic representation of the two salicylate binding sites in the dimer. (c) A representation of some of the binding site residues relative to the bound salicylate in the binding pocket. In the first binding site (SAL1), salicylate made distinct interactions with both Arg16 and Lys8. The electron density for the bound salicylates was obtained from a 2F[o] − F[c] composite omit map.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 377, 655-667) copyright 2008.

Figures were selected by an automated process.