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| | <StructureSection load='5oe4' size='340' side='right'caption='[[5oe4]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='5oe4' size='340' side='right'caption='[[5oe4]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oe4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OE4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OE4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oe4]] is a 2 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=5OE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OE4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3UK:5-O-[(S)-[(2-AMINOBENZOYL)OXY](HYDROXY)PHOSPHORYL]ADENOSINE'>3UK</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]] 1.904Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ligase Ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.32 6.2.1.32] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3UK:5-O-[(S)-[(2-AMINOBENZOYL)OXY](HYDROXY)PHOSPHORYL]ADENOSINE'>3UK</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=5oe4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oe4 OCA], [http://pdbe.org/5oe4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oe4 RCSB], [http://www.ebi.ac.uk/pdbsum/5oe4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oe4 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=5oe4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oe4 OCA], [https://pdbe.org/5oe4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oe4 RCSB], [https://www.ebi.ac.uk/pdbsum/5oe4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oe4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PQSA_PSEAE PQSA_PSEAE]] Catalyzes the formation of anthraniloyl-CoA, which is the priming step for entry into the Pseudomonas quinolone signal (PQS) biosynthetic pathway. Also active on a variety of aromatic substrates, including benzoate and chloro and fluoro derivatives of anthranilate.<ref>PMID:18083812</ref> <ref>PMID:18728009</ref> | + | [https://www.uniprot.org/uniprot/PQSA_PSEAE PQSA_PSEAE] Catalyzes the formation of anthraniloyl-CoA, which is the priming step for entry into the Pseudomonas quinolone signal (PQS) biosynthetic pathway. Also active on a variety of aromatic substrates, including benzoate and chloro and fluoro derivatives of anthranilate.<ref>PMID:18083812</ref> <ref>PMID:18728009</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ligase]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Blankenfeldt, W]] | + | [[Category: Blankenfeldt W]] |
| - | [[Category: Ewert, W]] | + | [[Category: Ewert W]] |
| - | [[Category: Witzgall, F]] | + | [[Category: Witzgall F]] |
| - | [[Category: Anl superfamily]]
| + | |
| - | [[Category: Anthranilate]]
| + | |
| - | [[Category: Anthraniloyl-amp]]
| + | |
| - | [[Category: Anthraniloyl-coa]]
| + | |
| - | [[Category: Aryl-coa ligase]]
| + | |
| - | [[Category: Pq]]
| + | |
| - | [[Category: Pqsa]]
| + | |
| - | [[Category: Pseudomonas aeruginosa]]
| + | |
| - | [[Category: Pseudomonas quinolone signal]]
| + | |
| - | [[Category: Quorum sensing]]
| + | |
| Structural highlights
Function
PQSA_PSEAE Catalyzes the formation of anthraniloyl-CoA, which is the priming step for entry into the Pseudomonas quinolone signal (PQS) biosynthetic pathway. Also active on a variety of aromatic substrates, including benzoate and chloro and fluoro derivatives of anthranilate.[1] [2]
Publication Abstract from PubMed
Pseudomonas aeruginosa, a prevalent pathogen in nosocomial infections and a major burden in cystic fibrosis, uses three interconnected quorum-sensing systems to coordinate virulence processes. At variance with other Gram-negatives, one of these systems relies on alkylquinolones (Pseudomonas Quinolone Signal, PQS) and may hence be an attractive target for new anti-infectives. Here, we report crystal structures of the N-terminal domain of anthranilate-CoA ligase PqsA, the first enzyme of PQS biosynthesis, in complex with anthraniloyl-AMP and 6-fluoroanthraniloyl-AMP (6FABA-AMP) at 1.4 and 1.7 A resolution. We find that PqsA belongs to an unrecognized subfamily of anthranilate-CoA ligases that recognizes the amino group of anthranilate through a water-mediated hydrogen bond. The complex with 6FABA-AMP explains why 6FABA, an inhibitor of PQS biosynthesis, is a good substrate of PqsA. Together, our data may pave a way to new pathoblockers in P. aeruginosa infections.
Structures of the N-terminal domain of PqsA in complex with anthraniloyl- and 6-fluoroanthraniloyl-AMP: substrate activation in Pseudomonas Quinolone Signal (PQS) biosynthesis.,Witzgall F, Ewert W, Blankenfeldt W Chembiochem. 2017 Aug 18. doi: 10.1002/cbic.201700374. PMID:28834007[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Coleman JP, Hudson LL, McKnight SL, Farrow JM 3rd, Calfee MW, Lindsey CA, Pesci EC. Pseudomonas aeruginosa PqsA is an anthranilate-coenzyme A ligase. J Bacteriol. 2008 Feb;190(4):1247-55. Epub 2007 Dec 14. PMID:18083812 doi:http://dx.doi.org/10.1128/JB.01140-07
- ↑ Zhang YM, Frank MW, Zhu K, Mayasundari A, Rock CO. PqsD is responsible for the synthesis of 2,4-dihydroxyquinoline, an extracellular metabolite produced by Pseudomonas aeruginosa. J Biol Chem. 2008 Oct 24;283(43):28788-94. doi: 10.1074/jbc.M804555200. Epub 2008, Aug 26. PMID:18728009 doi:http://dx.doi.org/10.1074/jbc.M804555200
- ↑ Witzgall F, Ewert W, Blankenfeldt W. Structures of the N-terminal domain of PqsA in complex with anthraniloyl- and 6-fluoroanthraniloyl-AMP: substrate activation in Pseudomonas Quinolone Signal (PQS) biosynthesis. Chembiochem. 2017 Aug 18. doi: 10.1002/cbic.201700374. PMID:28834007 doi:http://dx.doi.org/10.1002/cbic.201700374
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