LigPlot of the wild type tetrapeptide ligand in the active site of <i>Haemophilus influenzae</i> OASS.

<p>The interactions between the Asn-Leu-Asn-Ile tetrapeptide and the active site residues of <i>H. influenzae</i> OASS-A (PDB code: 1Y7L) are reported. The figure was drawn with LigPlot program version 4.5.3 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077558#pone.0077558-Laskowski1" target="_blank">[124]</a>.</p

List of compounds selected from virtual screening and tested against OASS-B.

*<p>due to the strong emission at 500 nm for excitation at 412 nm, this compound was assayed at concentrations lower than 100 µM and no binding was observed.</p

Compounds selected by SBVS/LBVS-docking procedures for OASS-A and OASS-B.

<p>Compounds selected by SBVS/LBVS-docking procedures for OASS-A and OASS-B.</p

GRID MIFs calculated for OASS-A and OASS-B.

<p>Red, blue and green contours identify the hydrogen bond acceptor, hydrogen bond donor and hydrophobic MIFs, respectively, calculated for OASS-A (pink cartoons) towards OASS-B (cyan cartoons). In <b>Panel B</b> compounds <b>1</b> and <b>13</b> are shown in ball and stick.</p

List of compounds tested against both OASS-A and OASS-B.

<p>List of compounds tested against both OASS-A and OASS-B.</p

Best HINT scored conformations of the compounds selected by the LBVS/docking procedures for OASS-B.

<p>The images were prepared with PyMOL (The PyMOL Molecular Graphics System, Version 1.5.0.4 Schrödinger, LLC.)</p

Structural comparison of OASS-A and OASS-B.

<p><b>Panel A</b>: Structure-based amino acid sequence alignment of OASS-A and OASS-B from <i>Salmonella typhimurium</i>. The alignment, carried out on the PDB entries 1OAS and 2JC3 using the Flexible structure AlignmenT (FATCAT) method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077558#pone.0077558-Ye1" target="_blank">[122]</a>, gave an overall identity of 40.32% and a similarity of 56.51%. Identical residues have a red background and residues with similar physicochemical properties are shown in red. Similarity scores were calculated by the ESPript program <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077558#pone.0077558-Gouet1" target="_blank">[123]</a> using the Blosum62 matrix set at global score of 0.2. Residues of the first active site shell are indicated by dark circles below the alignment. <b>Panel B</b>: Active site of OASS-A. Residues of the first active site shell and PLP are shown in ball and stick style, colored pink and yellow, respectively. <b>Panel C</b>: Active site of OASS-B. Residues of the first active site shell and PLP are shown in ball and stick style, colored cyan and yellow, respectively.</p

List of compounds selected from virtual screening and tested against OASS-A.

<p>List of compounds selected from virtual screening and tested against OASS-A.</p

Docking pose of best binders to the two isozymes placed into the active sites.

<p><b>Panel A</b>: Docking pose of <b>1</b> in the OASS-A binding pocket. Red and green contours identify the hydrogen bond acceptor and hydrophobic GRID MIFs. Hydrogen bond donor hot spots have not been shown for clarity. <b>Panel B</b>: Docking pose of compound <b>13</b> in the OASS-B binding pocket. Red and green contours identify the hydrogen bond acceptor and hydrophobic GRID MIFs. Hydrogen bond donor hot spots have not been shown for clarity.</p

Cysteine biosynthesis.

<p><b>Upper panel</b>: Intermediates of cysteine biosynthesis in mammals and bacteria. The red arrows indicate the biosynthetic pathway in mammals and the yellow arrows the biosynthetic pathway in bacteria. <b>Lower panel</b>: Sulfur assimilation in bacteria. Sulfate and thiosulfate are the most abundant forms of extracellular sulfur, the latter being predominant under less oxidizing conditions. Inorganic sulfur enters the cells through specific transporters. In contrast to OASS-A, OASS-B can directly use thiosulfate for cysteine biosynthesis. The product S-sulfo-L-cysteine is reduced by glutaredoxins to cysteine and sulfide that enters in the last step of the sulfate reduction pathway <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077558#pone.0077558-Sekowska1" target="_blank">[120]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077558#pone.0077558-Hatzios2" target="_blank">[121]</a>.</p