Limits...
Crystal structure of Bacillus cereus HlyIIR, a transcriptional regulator of the gene for pore-forming toxin hemolysin II.

Kovalevskiy OV, Lebedev AA, Surin AK, Solonin AS, Antson AA - J. Mol. Biol. (2006)

Bottom Line: We show that HlyIIR forms a tight dimer with a fold and overall architecture similar to the TetR family of repressors.A remarkable feature of the structure is a large internal cavity with a volume of 550 A(3) suggesting that the activity of HlyIIR is modulated by binding of a ligand, which triggers the toxin production.Based on structural data and previous biochemical evidence, we propose a model for HlyIIR interaction with the DNA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.

ABSTRACT
Production of Bacillus cereus and Bacillus anthracis toxins is controlled by a number of transcriptional regulators. Here we report the crystal structure of B. cereus HlyIIR, a regulator of the gene encoding the pore-forming toxin hemolysin II. We show that HlyIIR forms a tight dimer with a fold and overall architecture similar to the TetR family of repressors. A remarkable feature of the structure is a large internal cavity with a volume of 550 A(3) suggesting that the activity of HlyIIR is modulated by binding of a ligand, which triggers the toxin production. Virtual ligand library screening shows that this pocket can accommodate compounds with molecular masses of up to 400-500 Da. Based on structural data and previous biochemical evidence, we propose a model for HlyIIR interaction with the DNA.

Show MeSH

Related in: MedlinePlus

The HlyIIR structure. (a) Electron density corresponding to one of the protein helices (α1) calculated with maximum likelihood weighted coefficients 2/Fo/–/Fc/ and contoured at 1.25σ. (b) and (c) Ribbon diagrams of HlyIIR. Monomer (b) is rainbow-coloured with its N-terminal in red and C-terminal in blue. Dotted line indicates the disordered segment, which was not modelled. The biological dimer (c) is generated by the crystallographic 2-fold axis. The large internal cavity (yellow) is drawn along the van der Waals radii of cavity-forming residues. The cavity surface was calculated by SURFNET.33 This Figure and Figures 3 and 4 were prepared using CCP4MG.34
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1828608&req=5

fig1: The HlyIIR structure. (a) Electron density corresponding to one of the protein helices (α1) calculated with maximum likelihood weighted coefficients 2/Fo/–/Fc/ and contoured at 1.25σ. (b) and (c) Ribbon diagrams of HlyIIR. Monomer (b) is rainbow-coloured with its N-terminal in red and C-terminal in blue. Dotted line indicates the disordered segment, which was not modelled. The biological dimer (c) is generated by the crystallographic 2-fold axis. The large internal cavity (yellow) is drawn along the van der Waals radii of cavity-forming residues. The cavity surface was calculated by SURFNET.33 This Figure and Figures 3 and 4 were prepared using CCP4MG.34

Mentions: The structure was determined by multi-wavelength anomalous dispersion (MAD) with selenomethionine (SeMet) HlyIIR (Table 1; Figure 1), since a molecular replacement approach with the closest structural homologue (E. coli Ycdc protein; PDB code 1PB6; 22% overall sequence identity) did not lead to structure solution. In the final model refined at 2.4 Å resolution all residues are within the most favoured and additionally allowed regions of the Ramachandran plot, with all stereochemical values within or better than the expected range.12 The model contains 179 amino acid residues (Ser4–Lys198) except for a segment of 16 residues (Leu170–Glu185) for which there was no clear electron density.


Crystal structure of Bacillus cereus HlyIIR, a transcriptional regulator of the gene for pore-forming toxin hemolysin II.

Kovalevskiy OV, Lebedev AA, Surin AK, Solonin AS, Antson AA - J. Mol. Biol. (2006)

The HlyIIR structure. (a) Electron density corresponding to one of the protein helices (α1) calculated with maximum likelihood weighted coefficients 2/Fo/–/Fc/ and contoured at 1.25σ. (b) and (c) Ribbon diagrams of HlyIIR. Monomer (b) is rainbow-coloured with its N-terminal in red and C-terminal in blue. Dotted line indicates the disordered segment, which was not modelled. The biological dimer (c) is generated by the crystallographic 2-fold axis. The large internal cavity (yellow) is drawn along the van der Waals radii of cavity-forming residues. The cavity surface was calculated by SURFNET.33 This Figure and Figures 3 and 4 were prepared using CCP4MG.34
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1828608&req=5

fig1: The HlyIIR structure. (a) Electron density corresponding to one of the protein helices (α1) calculated with maximum likelihood weighted coefficients 2/Fo/–/Fc/ and contoured at 1.25σ. (b) and (c) Ribbon diagrams of HlyIIR. Monomer (b) is rainbow-coloured with its N-terminal in red and C-terminal in blue. Dotted line indicates the disordered segment, which was not modelled. The biological dimer (c) is generated by the crystallographic 2-fold axis. The large internal cavity (yellow) is drawn along the van der Waals radii of cavity-forming residues. The cavity surface was calculated by SURFNET.33 This Figure and Figures 3 and 4 were prepared using CCP4MG.34
Mentions: The structure was determined by multi-wavelength anomalous dispersion (MAD) with selenomethionine (SeMet) HlyIIR (Table 1; Figure 1), since a molecular replacement approach with the closest structural homologue (E. coli Ycdc protein; PDB code 1PB6; 22% overall sequence identity) did not lead to structure solution. In the final model refined at 2.4 Å resolution all residues are within the most favoured and additionally allowed regions of the Ramachandran plot, with all stereochemical values within or better than the expected range.12 The model contains 179 amino acid residues (Ser4–Lys198) except for a segment of 16 residues (Leu170–Glu185) for which there was no clear electron density.

Bottom Line: We show that HlyIIR forms a tight dimer with a fold and overall architecture similar to the TetR family of repressors.A remarkable feature of the structure is a large internal cavity with a volume of 550 A(3) suggesting that the activity of HlyIIR is modulated by binding of a ligand, which triggers the toxin production.Based on structural data and previous biochemical evidence, we propose a model for HlyIIR interaction with the DNA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.

ABSTRACT
Production of Bacillus cereus and Bacillus anthracis toxins is controlled by a number of transcriptional regulators. Here we report the crystal structure of B. cereus HlyIIR, a regulator of the gene encoding the pore-forming toxin hemolysin II. We show that HlyIIR forms a tight dimer with a fold and overall architecture similar to the TetR family of repressors. A remarkable feature of the structure is a large internal cavity with a volume of 550 A(3) suggesting that the activity of HlyIIR is modulated by binding of a ligand, which triggers the toxin production. Virtual ligand library screening shows that this pocket can accommodate compounds with molecular masses of up to 400-500 Da. Based on structural data and previous biochemical evidence, we propose a model for HlyIIR interaction with the DNA.

Show MeSH
Related in: MedlinePlus