4AKY

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

Summary for 4AKY

• Entry DOI: 10.2210/pdb4aky/pdb
• Related: 2BHM 4AKZ
• Descriptor: TYPE IV SECRETION SYSTEM PROTEIN VIRB8, 2-(butylamino)quinolin-8-ol (3 entities in total)
• Functional Keywords: transport protein, bacterial type iv secretion
• Biological source: BRUCELLA SUIS
• Cellular location: Cell inner membrane; Single-pass membrane protein (Potential): Q7CEG3
• Total number of polymer chains: 5
• Total formula weight: 78761.93

Authors

Coincon, M.,Smith, M.A.,Sygusch, J.,Baron, C. (deposition date: 2012-02-29, release date: 2012-09-05, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)