6d6c: Difference between revisions
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The | ==The structure of ligand binding domain of LasR in complex with TP-1 homolog, compound 12== | ||
<StructureSection load='6d6c' size='340' side='right' caption='[[6d6c]], [[Resolution|resolution]] 1.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6d6c]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D6C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D6C FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FYD:2,4-dibromo-6-{[(2-nitrobenzene-1-carbonyl)amino]methyl}phenyl+2-methoxybenzoate'>FYD</scene>, <scene name='pdbligand=HIS:HISTIDINE'>HIS</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6d6a|6d6a]], [[6d6b|6d6b]]</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=6d6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d6c OCA], [http://pdbe.org/6d6c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d6c RCSB], [http://www.ebi.ac.uk/pdbsum/6d6c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d6c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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;"> | |||
== 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<ref>PMID:30033130</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Nair, S | <div class="pdbe-citations 6d6c" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dong, S H]] | |||
[[Category: Nair, S K]] | |||
[[Category: Luxr receptor]] | |||
[[Category: Signaling protein-agonist complex]] | |||
Revision as of 00:48, 10 August 2018
The structure of ligand binding domain of LasR in complex with TP-1 homolog, compound 12The structure of ligand binding domain of LasR in complex with TP-1 homolog, compound 12
Structural highlights
Function[LASR_PSEAE] Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer. Publication Abstract from PubMedChemical 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. References
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