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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.

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Ligand-binding pocket. (a) Stereo view with the cavity contoured as in Figure 1(c) and cavity-lining residues shown by sticks. The compound that gave a highest score during the AutoDock screening (NCI 23904) is shown with its carbon atoms in brown, oxygen atoms in pink and nitrogen atoms in light blue. (b) Difference electron density maps (green) corresponding to the pocket area and contoured at 3σ.
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fig3: Ligand-binding pocket. (a) Stereo view with the cavity contoured as in Figure 1(c) and cavity-lining residues shown by sticks. The compound that gave a highest score during the AutoDock screening (NCI 23904) is shown with its carbon atoms in brown, oxygen atoms in pink and nitrogen atoms in light blue. (b) Difference electron density maps (green) corresponding to the pocket area and contoured at 3σ.

Mentions: An important feature of the HlyIIR structure is a large internal cavity in the C-terminal α-helical bundle. This cavity is 18 Å long and has an internal volume of ∼ 550 Å3 (Figure 3). It is only partially filled by electron density (Figure 3(b)), which appears to correspond to solvent molecules or crystallisation buffer components, since mass-spectrometry analysis did not reveal any compounds bound to the protein (data not shown). Most of the inner surface of the cavity is lined by 25 hydrophobic residues (Figure 3(a)) contributed by helices α4–α8. It is likely that the entrance to the ligand binding pocket is formed by helices α4 and α5 and closed by side-chains of Tyr62 and His93 and main-chain atoms of helix α4.


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)

Ligand-binding pocket. (a) Stereo view with the cavity contoured as in Figure 1(c) and cavity-lining residues shown by sticks. The compound that gave a highest score during the AutoDock screening (NCI 23904) is shown with its carbon atoms in brown, oxygen atoms in pink and nitrogen atoms in light blue. (b) Difference electron density maps (green) corresponding to the pocket area and contoured at 3σ.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Ligand-binding pocket. (a) Stereo view with the cavity contoured as in Figure 1(c) and cavity-lining residues shown by sticks. The compound that gave a highest score during the AutoDock screening (NCI 23904) is shown with its carbon atoms in brown, oxygen atoms in pink and nitrogen atoms in light blue. (b) Difference electron density maps (green) corresponding to the pocket area and contoured at 3σ.
Mentions: An important feature of the HlyIIR structure is a large internal cavity in the C-terminal α-helical bundle. This cavity is 18 Å long and has an internal volume of ∼ 550 Å3 (Figure 3). It is only partially filled by electron density (Figure 3(b)), which appears to correspond to solvent molecules or crystallisation buffer components, since mass-spectrometry analysis did not reveal any compounds bound to the protein (data not shown). Most of the inner surface of the cavity is lined by 25 hydrophobic residues (Figure 3(a)) contributed by helices α4–α8. It is likely that the entrance to the ligand binding pocket is formed by helices α4 and α5 and closed by side-chains of Tyr62 and His93 and main-chain atoms of helix α4.

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