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| | ==The structure of ligand binding domain of LasR in complex with TP-1 homolog, compound 16== | | ==The structure of ligand binding domain of LasR in complex with TP-1 homolog, compound 16== |
| - | <StructureSection load='6d6n' size='340' side='right' caption='[[6d6n]], [[Resolution|resolution]] 1.81Å' scene=''> | + | <StructureSection load='6d6n' size='340' side='right'caption='[[6d6n]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d6n]] is a 4 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=6D6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D6N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d6n]] is a 4 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=6D6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D6N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FXJ:2,4-dibromo-6-{[(2-nitrobenzene-1-carbonyl)amino]methyl}phenyl+4-methoxybenzoate'>FXJ</scene>, <scene name='pdbligand=PHE:PHENYLALANINE'>PHE</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]] 1.81Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6d6b|6d6b]], [[6d6c|6d6c]], [[6d6d|6d6d]], [[6d6l|6d6l]], [[6d6m|6d6m]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FXJ:2,4-dibromo-6-{[(2-nitrobenzene-1-carbonyl)amino]methyl}phenyl+4-methoxybenzoate'>FXJ</scene>, <scene name='pdbligand=PHE:PHENYLALANINE'>PHE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lasR, PA1430 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</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=6d6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d6n OCA], [https://pdbe.org/6d6n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d6n RCSB], [https://www.ebi.ac.uk/pdbsum/6d6n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d6n ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6d6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d6n OCA], [http://pdbe.org/6d6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d6n RCSB], [http://www.ebi.ac.uk/pdbsum/6d6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d6n ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LASR_PSEAE LASR_PSEAE]] Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer. | + | [https://www.uniprot.org/uniprot/LASR_PSEAE LASR_PSEAE] Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Transcriptional activator|Transcriptional activator]] | + | *[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pseae]] | + | [[Category: Large Structures]] |
| - | [[Category: Dong, S H]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Nair, S K]] | + | [[Category: Dong SH]] |
| - | [[Category: Luxr receptor]] | + | [[Category: Nair SK]] |
| - | [[Category: Signaling protein-agonist complex]]
| + | |
| Structural highlights
Function
LASR_PSEAE Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer.
Publication Abstract from PubMed
Chemical strategies to block quorum sensing (QS) could provide a route to attenuate virulence in bacterial pathogens. Considerable research has focused on this approach in Pseudomonas aeruginosa, which uses the LuxR-type receptor LasR to regulate much of its QS network. Non-native ligands that antagonize LasR have been developed, yet we have little understanding of the mode by which these compounds interact with LasR and alter its function, as the receptor is unstable in their presence. Herein, we report an approach to circumvent this challenge through the study of a series of synthetic LasR agonists with varying levels of potency. Structural investigations of these ligands with the LasR ligand-binding domain reveal that certain agonists can enforce a conformation that deviates from that observed for other, often more potent agonists. These results, when combined with cell-based and biophysical analyses, suggest a functional model for LasR that could guide future ligand design.
Structural and Biochemical Studies of Non-native Agonists of the LasR Quorum-Sensing Receptor Reveal an L3 Loop "Out" Conformation for LasR.,O'Reilly MC, Dong SH, Rossi FM, Karlen KM, Kumar RS, Nair SK, Blackwell HE Cell Chem Biol. 2018 Jul 11. pii: S2451-9456(18)30221-6. doi:, 10.1016/j.chembiol.2018.06.007. PMID:30033130[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ O'Reilly MC, Dong SH, Rossi FM, Karlen KM, Kumar RS, Nair SK, Blackwell HE. Structural and Biochemical Studies of Non-native Agonists of the LasR Quorum-Sensing Receptor Reveal an L3 Loop "Out" Conformation for LasR. Cell Chem Biol. 2018 Jul 11. pii: S2451-9456(18)30221-6. doi:, 10.1016/j.chembiol.2018.06.007. PMID:30033130 doi:http://dx.doi.org/10.1016/j.chembiol.2018.06.007
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