6D6C

The structure of ligand binding domain of LasR in complex with TP-1 homolog, compound 12

6D6C の概要

• エントリーDOI: 10.2210/pdb6d6c/pdb
• 関連するPDBエントリー: 6D6A 6D6B
• 分子名称: Transcriptional activator protein LasR, 2,4-dibromo-6-{[(2-nitrobenzene-1-carbonyl)amino]methyl}phenyl 2-methoxybenzoate, HISTIDINE, ... (4 entities in total)
• 機能のキーワード: luxr receptor, signaling protein-agonist complex, signaling protein/agonist
• 由来する生物種: Pseudomonas aeruginosa PAO1
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 235027.95

構造登録者

Dong, S.H.,Nair, S.K. (登録日: 2018-04-20, 公開日: 2018-08-08, 最終更新日: 2024-03-13)

主引用文献

O'Reilly, M.C.,Dong, S.H.,Rossi, F.M.,Karlen, K.M.,Kumar, R.S.,Nair, S.K.,Blackwell, H.E.
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, 25:1128-1139.e3, 2018

PubMed Abstract: 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.

PubMed: 30033130
DOI: 10.1016/j.chembiol.2018.06.007

実験手法

X-RAY DIFFRACTION (1.88 Å)