2WYE
The quorum quenching N-acyl homoserine lactone acylase PvdQ is an Ntn- Hydrolase with an unusual substrate-binding pocket
Summary for 2WYE
| Entry DOI | 10.2210/pdb2wye/pdb |
| Related | 2WYB 2WYC 2WYD |
| Descriptor | ACYL-HOMOSERINE LACTONE ACYLASE PVDQ SUBUNIT ALPHA, ACYL-HOMOSERINE LACTONE ACYLASE PVDQ SUBUNIT BETA, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | zymogen, hydrolase, periplasm |
| Biological source | PSEUDOMONAS AERUGINOSA More |
| Cellular location | Periplasm (Probable): Q9I194 Q9I194 |
| Total number of polymer chains | 2 |
| Total formula weight | 79727.49 |
| Authors | Bokhove, M.,Nadal Jimenez, P.,Quax, W.J.,Dijkstra, B.W. (deposition date: 2009-11-16, release date: 2009-12-29, Last modification date: 2024-10-23) |
| Primary citation | Bokhove, M.,Nadal Jimenez, P.,Quax, W.J.,Dijkstra, B.W. The Quorum-Quenching N-Acyl Homoserine Lactone Acylase Pvdq is an Ntn-Hydrolase with an Unusual Substrate-Binding Pocket Proc.Natl.Acad.Sci.USA, 107:686-, 2010 Cited by PubMed Abstract: In many Gram-negative pathogens, their virulent behavior is regulated by quorum sensing, in which diffusible signals such as N-acyl homoserine lactones (AHLs) act as chemical messaging compounds. Enzymatic degradation of these diffusible signals by, e.g., lactonases or amidohydrolases abolishes AHL regulated virulence, a process known as quorum quenching. Here we report the first crystal structure of an AHL amidohydrolase, the AHL acylase PvdQ from Pseudomonas aeruginosa. PvdQ has a typical alpha/beta heterodimeric Ntn-hydrolase fold, similar to penicillin G acylase and cephalosporin acylase. However, it has a distinct, unusually large, hydrophobic binding pocket, ideally suited to recognize C12 fatty acid-like chains of AHLs. Binding of a C12 fatty acid or a 3-oxo-C12 fatty acid induces subtle conformational changes to accommodate the aliphatic chain. Furthermore, the structure of a covalent ester intermediate identifies Serbeta1 as the nucleophile and Asnbeta269 and Valbeta70 as the oxyanion hole residues in the AHL degradation process. Our structures show the versatility of the Ntn-hydrolase scaffold and can serve as a structural paradigm for Ntn-hydrolases with similar substrate preference. Finally, the quorum-quenching capabilities of PvdQ may be utilized to suppress the quorum-sensing machinery of pathogens. PubMed: 20080736DOI: 10.1073/PNAS.0911839107 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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