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5hiq

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Crystal Structure of PQS Response Protein PqsE in Complex with 2-(1H-pyrrol-1-yl)benzoic acid

Structural highlights

5hiq is a 1 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PQSE_PSEAE Required for the biosynthesis of the quorum-sensing signaling molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS), which are important for biofilm formation and virulence. Catalyzes the hydrolysis of the intermediate 2-aminobenzoylacetyl-CoA (2-ABA-CoA) to form 2-aminobenzoylacetate (2-ABA), the precursor of HHQ. In vitro, can also hydrolyze other substrates such as S-ethyl-acetothioacetate and acetoacetyl-CoA, but is inactive against anthraniloyl-CoA, malonyl-CoA and octanoyl-CoA (PubMed:25960261, PubMed:27082157). Beyond its thioesterase function, is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development (PubMed:27851827).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Pseudomonas aeruginosa uses quorum sensing (QS) as a cell-to-cell communication system to orchestrate the expression of virulence determinants. The biosynthesis of the important Pseudomonas quinolone signal (PQS) requires the pqsABCDE operon. Here, PqsE acts as a pathway-specific thioesterase, but it also contributes to the regulation of bacterial virulence via an unknown mechanism. In this manuscript, we report the discovery of PqsE inhibitors as tool compounds to gain further insights into its different functions. Differential scanning fluorimetry (DSF) was used to screen a fragment library, and isothermal titration calorimetry (ITC) was employed as a secondary filter. As proven by X-ray crystallography, hit molecules bound to the active center inhibiting PqsE's thioesterase activity in cell-based and in vitro assays. Notably, the ligands did not affect the levels of the PqsE-regulated virulence factor pyocyanin. These findings indicate that the regulatory function of PqsE is not linked to its thioesterase activity and must be encoded outside of the active center. This study highlights the potential of fragment-based screening for the discovery of tool compounds. This approach provided novel insight into complex biological systems, which could not be obtained by knockout studies.

Dissecting the Multiple Roles of PqsE in Pseudomonas aeruginosa Virulence by Discovery of Small Tool Compounds.,Zender M, Witzgall F, Drees SL, Weidel E, Maurer CK, Fetzner S, Blankenfeldt W, Empting M, Hartmann RW ACS Chem Biol. 2016 Apr 28. PMID:27082157^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Drees SL, Fetzner S. PqsE of Pseudomonas aeruginosa Acts as Pathway-Specific Thioesterase in the Biosynthesis of Alkylquinolone Signaling Molecules. Chem Biol. 2015 May 21;22(5):611-8. doi: 10.1016/j.chembiol.2015.04.012. Epub , 2015 May 7. PMID:25960261 doi:http://dx.doi.org/10.1016/j.chembiol.2015.04.012
↑ Zender M, Witzgall F, Drees SL, Weidel E, Maurer CK, Fetzner S, Blankenfeldt W, Empting M, Hartmann RW. Dissecting the Multiple Roles of PqsE in Pseudomonas aeruginosa Virulence by Discovery of Small Tool Compounds. ACS Chem Biol. 2016 Apr 28. PMID:27082157 doi:http://dx.doi.org/10.1021/acschembio.6b00156
↑ Rampioni G, Falcone M, Heeb S, Frangipani E, Fletcher MP, Dubern JF, Visca P, Leoni L, Camara M, Williams P. Unravelling the Genome-Wide Contributions of Specific 2-Alkyl-4-Quinolones and PqsE to Quorum Sensing in Pseudomonas aeruginosa. PLoS Pathog. 2016 Nov 16;12(11):e1006029. doi: 10.1371/journal.ppat.1006029. , eCollection 2016 Nov. PMID:27851827 doi:http://dx.doi.org/10.1371/journal.ppat.1006029
↑ Zender M, Witzgall F, Drees SL, Weidel E, Maurer CK, Fetzner S, Blankenfeldt W, Empting M, Hartmann RW. Dissecting the Multiple Roles of PqsE in Pseudomonas aeruginosa Virulence by Discovery of Small Tool Compounds. ACS Chem Biol. 2016 Apr 28. PMID:27082157 doi:http://dx.doi.org/10.1021/acschembio.6b00156

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5hiq"

Categories: Large Structures | Pseudomonas aeruginosa PAO1 | Blankenfeldt W | Witzgall F

@@ Line 3: / Line 3: @@
 <StructureSection load='5hiq' size='340' side='right'caption='[[5hiq]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hiq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HIQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HIQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hiq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HIQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=60Q:2-PYRROL-1-YLBENZOIC+ACID'>60Q</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA1000 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=60Q:2-PYRROL-1-YLBENZOIC+ACID'>60Q</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hiq OCA], [http://pdbe.org/5hiq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hiq RCSB], [http://www.ebi.ac.uk/pdbsum/5hiq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hiq ProSAT]</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=5hiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hiq OCA], [https://pdbe.org/5hiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hiq RCSB], [https://www.ebi.ac.uk/pdbsum/5hiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hiq ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PQSE_PSEAE PQSE_PSEAE] Required for the biosynthesis of the quorum-sensing signaling molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS), which are important for biofilm formation and virulence. Catalyzes the hydrolysis of the intermediate 2-aminobenzoylacetyl-CoA (2-ABA-CoA) to form 2-aminobenzoylacetate (2-ABA), the precursor of HHQ. In vitro, can also hydrolyze other substrates such as S-ethyl-acetothioacetate and acetoacetyl-CoA, but is inactive against anthraniloyl-CoA, malonyl-CoA and octanoyl-CoA (PubMed:25960261, PubMed:27082157). Beyond its thioesterase function, is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development (PubMed:27851827).<ref>PMID:25960261</ref> <ref>PMID:27082157</ref> <ref>PMID:27851827</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Pseae]]
+[[Category: Pseudomonas aeruginosa PAO1]]
-[[Category: Blankenfeldt, W]]
+[[Category: Blankenfeldt W]]
-[[Category: Witzgall, F]]
+[[Category: Witzgall F]]
-[[Category: Inhibitor]]
-[[Category: Metal binding protein]]
-[[Category: Pq]]
-[[Category: Pqse]]
-[[Category: Pseudomona]]
-[[Category: Quorum sensing]]

5hiq

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Current revision

Crystal Structure of PQS Response Protein PqsE in Complex with 2-(1H-pyrrol-1-yl)benzoic acid

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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