6et1

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of PqsBC from Pseudomonas aeruginosa (crystal form 2)

Structural highlights

6et1 is a 8 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 2.65Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PQSC_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. The PqsC/PqsB complex catalyzes the condensation of 2-aminobenzoylacetate (2-ABA) and octanoyl-CoA to form HHQ. First, PqsC acquires an octanoyl group from octanoyl-CoA and forms an octanoyl-PqsC intermediate. Then, together with PqsB, it catalyzes the coupling of 2-ABA with the octanoate group, leading to decarboxylation and dehydration, and resulting in closure of the quinoline ring.^[1] ^[2]

Publication Abstract from PubMed

Pseudomonas aeruginosa is a bacterial pathogen that causes life-threatening infections in immunocompromised patients. It produces a large armory of saturated and mono-unsaturated 2-alkyl-4(1H)-quinolones (AQs) and AQ N-oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the beta-ketoacyl-acyl-carrier protein synthase III (FabH)-like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2-heptyl-4(1H)-quinolone (HHQ), by condensing octanoyl-coenzyme A (CoA) with 2-aminobenzoylacetate (2-ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium-chain acyl-CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono-unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 A resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl-binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH-enzymes, for which such structural transitions have been postulated but have never been observed.

The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH-like 2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) Biosynthesis Enzyme PqsBC.,Witzgall F, Depke T, Hoffmann M, Empting M, Bronstrup M, Muller R, Blankenfeldt W Chembiochem. 2018 May 3. doi: 10.1002/cbic.201800153. PMID:29722462^[3]

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

References

↑ Dulcey CE, Dekimpe V, Fauvelle DA, Milot S, Groleau MC, Doucet N, Rahme LG, Lepine F, Deziel E. The end of an old hypothesis: the pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids. Chem Biol. 2013 Dec 19;20(12):1481-91. doi: 10.1016/j.chembiol.2013.09.021. Epub , 2013 Nov 14. PMID:24239007 doi:http://dx.doi.org/10.1016/j.chembiol.2013.09.021
↑ Drees SL, Li C, Prasetya F, Saleem M, Dreveny I, Williams P, Hennecke U, Emsley J, Fetzner S. PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism. J Biol Chem. 2016 Jan 25. pii: jbc.M115.708453. PMID:26811339 doi:http://dx.doi.org/10.1074/jbc.M115.708453
↑ Witzgall F, Depke T, Hoffmann M, Empting M, Bronstrup M, Muller R, Blankenfeldt W. The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH-like 2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) Biosynthesis Enzyme PqsBC. Chembiochem. 2018 May 3. doi: 10.1002/cbic.201800153. PMID:29722462 doi:http://dx.doi.org/10.1002/cbic.201800153

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/6et1"

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

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6et1 is ON HOLD  until Paper Publication
+==Crystal structure of PqsBC from Pseudomonas aeruginosa (crystal form 2)==
+<StructureSection load='6et1' size='340' side='right'caption='[[6et1]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6et1]] is a 8 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=6ET1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ET1 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]] 2.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=6et1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6et1 OCA], [https://pdbe.org/6et1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6et1 RCSB], [https://www.ebi.ac.uk/pdbsum/6et1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6et1 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PQSC_PSEAE PQSC_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. The PqsC/PqsB complex catalyzes the condensation of 2-aminobenzoylacetate (2-ABA) and octanoyl-CoA to form HHQ. First, PqsC acquires an octanoyl group from octanoyl-CoA and forms an octanoyl-PqsC intermediate. Then, together with PqsB, it catalyzes the coupling of 2-ABA with the octanoate group, leading to decarboxylation and dehydration, and resulting in closure of the quinoline ring.<ref>PMID:24239007</ref> <ref>PMID:26811339</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Pseudomonas aeruginosa is a bacterial pathogen that causes life-threatening infections in immunocompromised patients. It produces a large armory of saturated and mono-unsaturated 2-alkyl-4(1H)-quinolones (AQs) and AQ N-oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the beta-ketoacyl-acyl-carrier protein synthase III (FabH)-like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2-heptyl-4(1H)-quinolone (HHQ), by condensing octanoyl-coenzyme A (CoA) with 2-aminobenzoylacetate (2-ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium-chain acyl-CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono-unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 A resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl-binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH-enzymes, for which such structural transitions have been postulated but have never been observed.
-Authors:
+The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH-like 2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) Biosynthesis Enzyme PqsBC.,Witzgall F, Depke T, Hoffmann M, Empting M, Bronstrup M, Muller R, Blankenfeldt W Chembiochem. 2018 May 3. doi: 10.1002/cbic.201800153. PMID:29722462<ref>PMID:29722462</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6et1" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Pseudomonas aeruginosa PAO1]]
+[[Category: Blankenfeldt W]]
+[[Category: Witzgall F]]

6et1

From Proteopedia

Current revision

Crystal structure of PqsBC from Pseudomonas aeruginosa (crystal form 2)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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