4K2G
Structure of Pseudomonas aeruginosa PvdQ bound to BRD-A33442372
Summary for 4K2G
| Entry DOI | 10.2210/pdb4k2g/pdb |
| Related | 3SRA 3SRB 3SRC 4K2F |
| Descriptor | Acyl-homoserine lactone acylase PvdQ, 1,2-ETHANEDIOL, (2S)-(4-fluorophenyl)[6-(trifluoromethyl)pyridin-2-yl]ethanenitrile, ... (5 entities in total) |
| Functional Keywords | amidohydrolase, bacterial protein, catalytic domain, high-throughput screening assays, molecular sequence data, oligopeptides, small molecule libraries, structure-activity relationship, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Pseudomonas aeruginosa More |
| Cellular location | Periplasm (Probable): Q9I194 Q9I194 |
| Total number of polymer chains | 2 |
| Total formula weight | 80232.01 |
| Authors | Drake, E.J.,Wurst, J.M.,Theriault, J.R.,Munoz, B.,Gulick, A.M. (deposition date: 2013-04-09, release date: 2014-06-18, Last modification date: 2024-11-06) |
| Primary citation | Wurst, J.M.,Drake, E.J.,Theriault, J.R.,Jewett, I.T.,VerPlank, L.,Perez, J.R.,Dandapani, S.,Palmer, M.,Moskowitz, S.M.,Schreiber, S.L.,Munoz, B.,Gulick, A.M. Identification of Inhibitors of PvdQ, an Enzyme Involved in the Synthesis of the Siderophore Pyoverdine. Acs Chem.Biol., 9:1536-1544, 2014 Cited by PubMed Abstract: Pseudomonas aeruginosa produces the peptide siderophore pyoverdine, which is used to acquire essential Fe(3+) ions from the environment. PvdQ, an Ntn hydrolase, is required for the biosynthesis of pyoverdine. PvdQ knockout strains are not infectious in model systems, suggesting that disruption of siderophore production via PvdQ inhibition could be exploited as a target for novel antibacterial agents, by preventing cells from acquiring iron in the low iron environments of most biological settings. We have previously described a high-throughput screen to identify inhibitors of PvdQ that identified inhibitors with IC50 values of ∼100 μM. Here, we describe the discovery of ML318, a biaryl nitrile inhibitor of PvdQ acylase. ML318 inhibits PvdQ in vitro (IC50 = 20 nM) by binding in the acyl-binding site, as confirmed by the X-ray crystal structure of PvdQ bound to ML318. Additionally, the PvdQ inhibitor is active in a whole cell assay, preventing pyoverdine production and limiting the growth of P. aeruginosa under iron-limiting conditions. PubMed: 24824984DOI: 10.1021/cb5001586 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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