4AKY

CRYSTAL STRUCTURE OF VIRB8 FROM BRUCELLA SUIS IN COMPLEX WITH INTERACTION INHIBITOR 2-(butylamino)-8-quinolinol

4AKY の概要

• エントリーDOI: 10.2210/pdb4aky/pdb
• 関連するPDBエントリー: 2BHM 4AKZ
• 分子名称: TYPE IV SECRETION SYSTEM PROTEIN VIRB8, 2-(butylamino)quinolin-8-ol (3 entities in total)
• 機能のキーワード: transport protein, bacterial type iv secretion
• 由来する生物種: BRUCELLA SUIS
• 細胞内の位置: Cell inner membrane; Single-pass membrane protein (Potential): Q7CEG3
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 78761.93

構造登録者

Coincon, M.,Smith, M.A.,Sygusch, J.,Baron, C. (登録日: 2012-02-29, 公開日: 2012-09-05, 最終更新日: 2023-12-20)

主引用文献

Smith, M.A.,Coincon, M.,Paschos, A.,Jolicoeur, B.,Lavallee, P.,Sygusch, J.,Baron, C.
Identification of the Binding Site of Brucella Virb8 Interaction Inhibitors.
Chem.Biol., 19:1041-, 2012

PubMed Abstract: Secretion systems translocate virulence factors of many bacterial pathogens, enabling their survival inside the host organism. Consequently, inhibition strongly attenuates pathogenicity and can be considered a target for novel antimicrobial drugs. The type IV secretion system (T4SS) of the intracellular pathogen Brucella is a prerequisite for its virulence, and in this work we targeted the interactions of the essential assembly factor protein, VirB8, using small-molecule inhibitors. High-throughput screening identified several potent and specific inhibitors, and the target-binding site of these inhibitors was identified by X-ray crystallography, in silico docking, and analysis of the derivates of the inhibitor B8I-2. VirB8 interaction inhibitors bind to a surface groove opposite to the dimerization interface, and by varying the binding-site residues, we were able to determine which residues are required for inhibitor activity. E115 and K182 were found to be especially important, and changes at R114, Y229, and L151 also reduced inhibitor efficiency.

PubMed: 22921071
DOI: 10.1016/J.CHEMBIOL.2012.07.007

実験手法

X-RAY DIFFRACTION (2.6 Å)