4m1j: Difference between revisions
New page: '''Unreleased structure''' The entry 4m1j is ON HOLD Authors: Rui Wu, Kenneth Clevenger, Joyce Er, Walter L. Fast, Dali Liu Description: Crystal structure of Pseudomonas aeruginosa Pvd... |
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The | ==Crystal structure of Pseudomonas aeruginosa PvdQ in complex with a transition state analogue== | ||
<StructureSection load='4m1j' size='340' side='right'caption='[[4m1j]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4m1j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M1J FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B0S:TRIDECYLBORONIC+ACID'>B0S</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4m1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1j OCA], [https://pdbe.org/4m1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m1j RCSB], [https://www.ebi.ac.uk/pdbsum/4m1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1j 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Pseudomonas aeruginosa enzyme PvdQ can process different substrates involved in quorum-sensing or in siderophore biosynthesis. Substrate selectivity was evaluated using steady-state kinetic constants for hydrolysis of N-acyl-homoserine lactones (HSLs) and p-nitrophenyl fatty acid esters. PvdQ prefers substrates with alkyl chains between 12 and 14 carbons long that do not bear a 3-oxo substitution and is revealed here to have a relatively high specificity constant for selected N-acyl-HSLs (kcat/KM = 105 to 106 M-1 s-1). However, endogenous P. aeruginosa N-acyl-HSLs are >/=100-fold disfavored, supporting the conclusion that PvdQ was not primarily evolved to regulate endogenous quorum-sensing. PvdQ plays an essential biosynthetic role for the siderophore pyoverdine, on which P. aeruginosa depends for growth in iron-limited environments. A series of alkylboronate inhibitors was found to be reversible, competitive, and extremely potent (Ki >/= 190 pM). A 1.8 A X-ray structure shows that 1-tridecylboronic acid forms a monocovalent bond with the N-terminal beta-chain Ser residue in the PvdQ heterodimer, mimicking a reaction transition state. This boronic acid inhibits growth of P. aeruginosa in iron-limited media, reproducing the phenotype of a genetic pvdQ disruption, although co-administration of an efflux pump inhibitor is required to maintain growth inhibition. These findings support the strategy of designing boron-based inhibitors of siderophore biosynthetic enzymes to control P. aeruginosa infections. | |||
Rational Design of a Transition State Analogue with Picomolar Affinity for Pseudomonas aeruginosa PvdQ, a Siderophore Biosynthetic Enzyme.,Clevenger KD, Wu R, Er JA, Liu D, Fast W ACS Chem Biol. 2013 Aug 6. PMID:23883096<ref>PMID:23883096</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4m1j" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa]] | |||
[[Category: Clevenger K]] | |||
[[Category: Er J]] | |||
[[Category: Fast WL]] | |||
[[Category: Liu D]] | |||
[[Category: Wu R]] | |||