6fho: Difference between revisions
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==Crystal structure of pqsL, a probable FAD-dependent monooxygenase from Pseudomonas aeruginosa - new refinement== | ==Crystal structure of pqsL, a probable FAD-dependent monooxygenase from Pseudomonas aeruginosa - new refinement== | ||
<StructureSection load='6fho' size='340' side='right' caption='[[6fho]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='6fho' size='340' side='right'caption='[[6fho]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6fho]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6fho]] 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=6FHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FHO FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=6fho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fho OCA], [https://pdbe.org/6fho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fho RCSB], [https://www.ebi.ac.uk/pdbsum/6fho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fho ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9HWJ1_PSEAE Q9HWJ1_PSEAE] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Belviso | [[Category: Pseudomonas aeruginosa PAO1]] | ||
[[Category: Drees | [[Category: Belviso BD]] | ||
[[Category: Ernst | [[Category: Drees SL]] | ||
[[Category: Fetzner | [[Category: Ernst S]] | ||
[[Category: Hennecke | [[Category: Fetzner S]] | ||
[[Category: Jagmann | [[Category: Hennecke U]] | ||
[[Category: Jagmann N]] | |||
Latest revision as of 15:28, 9 May 2024
Crystal structure of pqsL, a probable FAD-dependent monooxygenase from Pseudomonas aeruginosa - new refinementCrystal structure of pqsL, a probable FAD-dependent monooxygenase from Pseudomonas aeruginosa - new refinement
Structural highlights
FunctionPublication Abstract from PubMedAlkyl hydroxyquinoline N-oxides (AQNOs) are antibiotic compounds produced by the opportunistic bacterial pathogen Pseudomonas aeruginosa They are products of the alkyl quinolone (AQ) biosynthetic pathway, which also generates the quorum sensing molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS). Although the enzymatic synthesis of HHQ and PQS had been elucidated, the route by which AQNOs are synthesized remained elusive. Here, we report on PqsL, the key enzyme for AQNO production, which structurally resembles class A flavoprotein monooxygenases such as p-hydroxybenzoate 3-hydroxylase (pHBH) and 3-hydroxybenzoate 6-hydroxylase. However, we found that unlike related enzymes, PqsL hydroxylates a primary aromatic amine group, and it does not use NAD(P)H as cosubstrate, but unexpectedly required reduced flavin as electron donor. We also observed that PqsL is active toward 2-aminobenzoylacetate (2-ABA), the central intermediate of the AQ pathway, and forms the unstable compound 2-hydroxylaminobenzoylacetate, which was preferred over 2-ABA as substrate of the downstream enzyme PqsBC. In vitro reconstitution of the PqsL/PqsBC reaction was feasible by using the FAD reductase HpaC, and we noted that the AQ:AQNO ratio is increased in an hpaC-deletion mutant of P. aeruginosa PAO1 compared with the ratio in the wild-type strain. A structural comparison with pHBH, the model enzyme of class A flavoprotein monooxygenases, revealed that structural features associated with NAD(P)H binding are missing in PqsL. Our study completes the AQNO biosynthetic pathway in P. aeruginosa, indicating that PqsL produces the unstable product 2-hydroxylaminobenzoylacetate from 2-ABA and depends on free reduced flavin as electron donor instead of NAD(P)H. PqsL uses reduced flavin to produce 2-hydroxylaminobenzoylacetate, a preferred PqsBC substrate in alkyl quinolone biosynthesis in Pseudomonas aeruginosa.,Drees SL, Ernst S, Belviso BD, Jagmann N, Hennecke U, Fetzner S J Biol Chem. 2018 Apr 18. pii: RA117.000789. doi: 10.1074/jbc.RA117.000789. PMID:29669807[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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