2wyc: Difference between revisions
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< | ==The quorum quenching N-acyl homoserine lactone acylase PvdQ in complex with 3-oxo-lauric acid== | ||
<StructureSection load='2wyc' size='340' side='right'caption='[[2wyc]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2wyc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WYC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3LA:3-OXODODECANOIC+ACID'>3LA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
--> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wyb|2wyb]], [[2wye|2wye]], [[2wyd|2wyd]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acyl-homoserine-lactone_acylase Acyl-homoserine-lactone acylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.97 3.5.1.97] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wyc OCA], [https://pdbe.org/2wyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wyc RCSB], [https://www.ebi.ac.uk/pdbsum/2wyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wyc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[https://www.uniprot.org/uniprot/PVDQ_PSEAE 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.<ref>PMID:16495538</ref> <ref>PMID:14532048</ref> <ref>PMID:12686626</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wy/2wyc_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wyc ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:20080736</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2wyc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acyl-homoserine-lactone acylase]] | [[Category: Acyl-homoserine-lactone acylase]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bokhove, M | [[Category: Pseae]] | ||
[[Category: Dijkstra, B W | [[Category: Bokhove, M]] | ||
[[Category: Jimenez, P Nadal | [[Category: Dijkstra, B W]] | ||
[[Category: Quax, W J | [[Category: Jimenez, P Nadal]] | ||
[[Category: Quax, W J]] | |||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Periplasm]] | [[Category: Periplasm]] | ||
[[Category: Zymogen]] | [[Category: Zymogen]] | ||
Latest revision as of 13:42, 13 April 2022
The quorum quenching N-acyl homoserine lactone acylase PvdQ in complex with 3-oxo-lauric acidThe quorum quenching N-acyl homoserine lactone acylase PvdQ in complex with 3-oxo-lauric acid
Structural highlights
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.[1] [2] [3] 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 PubMedIn 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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