7KGX

Structure of PQS Response Protein PqsE in Complex with 4-(3-(2-methyl-2-morpholinobutyl)ureido)-N-(thiazol-2-yl)benzamide

7KGX の概要

• エントリーDOI: 10.2210/pdb7kgx/pdb
• 関連するPDBエントリー: 7KGW
• 分子名称: 2-aminobenzoylacetyl-CoA thioesterase, FE (III) ION, 4-({[(2R)-2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}amino)-N-(1,3-thiazol-2-yl)benzamide, ... (4 entities in total)
• 機能のキーワード: quorum sensing, pqs, pqse, inhibitor, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35161.79

構造登録者

Jeffrey, P.D.,Taylor, I.R.,Bassler, B.L. (登録日: 2020-10-19, 公開日: 2021-05-05, 最終更新日: 2023-10-18)

主引用文献

Taylor, I.R.,Paczkowski, J.E.,Jeffrey, P.D.,Henke, B.R.,Smith, C.D.,Bassler, B.L.
Inhibitor Mimetic Mutations in the Pseudomonas aeruginosa PqsE Enzyme Reveal a Protein-Protein Interaction with the Quorum-Sensing Receptor RhlR That Is Vital for Virulence Factor Production.
Acs Chem.Biol., 16:740-752, 2021

PubMed Abstract: is an opportunistic human pathogen that causes fatal infections. There exists an urgent need for new antimicrobial agents to combat . We conducted a screen for molecules that bind the virulence-controlling protein PqsE and characterized hit compounds for inhibition of PqsE enzymatic activity. The binding conformations of two inhibitory molecules, BB391 and BB393, were identified by crystallography, and inhibitor binding was mimicked by the substitution of PqsE residues E182 and S285 with tryptophan. Comparison of the inhibitor-mimetic mutations to the catalytically inactive PqsE D73A protein demonstrated that catalysis is not responsible for the role PqsE plays in driving virulence factor production. Rather, the PqsE E182W protein fails to interact with the quorum-sensing receptor, RhlR, and our results suggest that it is this interaction that is responsible for promoting virulence factor production in . These findings provide a new route for drug discovery efforts targeting PqsE.

PubMed: 33793200
DOI: 10.1021/acschembio.1c00049

実験手法

X-RAY DIFFRACTION (2 Å)