2wye

THE QUORUM QUENCHING N-ACYL HOMOSERINE LACTONE ACYLASE PVDQ IS AN NTN-HYDROLASE WITH AN UNUSUAL SUBSTRATE-BINDING POCKET

spinqualitylabelsall models 2wye, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wye is a 2 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL Related: 2wyc, 2wyb, 2wyd Activity: Acyl-homoserine-lactone acylase, with EC number 3.5.1.97 Resources: FirstGlance, OCA, RCSB, PDBsum Function [PVDQ_PSEAE] Catalyzes the deacylation of acyl-homoserine lactone (AHL or acyl-HSL), releasing homoserine lactone (HSL) and the corresponding fatty acid. Possesses a specificity for the degradation of long-chain acyl-HSLs (side chains of 11 to 14 carbons in length). Degrades 3-oxo-C12-HSL, one of the two main AHL signal molecules of P.aeruginosa, and thereby functions as a quorum quencher, inhibiting the las quorum-sensing system. Therefore, may enable P.aeruginosa to modulate its own quorum-sensing-dependent pathogenic potential. Also appears to be required for pyoverdin biosynthesis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. The quorum-quenching N-acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket.,Bokhove M, Jimenez PN, Quax WJ, Dijkstra BW Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):686-91. Epub 2009 Dec 22. PMID:20080736 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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