Crystals of LuxP and complexes thereof

Abstract

A crystal comprising LuxP is obtained, and a binding site for autoinducer-2 (AI-2) identified. The X-ray crystallographic data for LuxP and a LuxP-AI-2 complex is determined and used in a drug discovery method. Pharmaceutical compositions comprising ligands identified by such drug discovery methods are used to treat bacterial infections.

1 . A crystal comprising LuxP.  
     
     
         2 . The crystal of  claim 1  comprising a LuxP-ligand complex, the crystal diffracting X-rays to a resolution of greater than 5.0 Angstroms.  
     
     
         3 . The crystal of  claim 2  wherein the resolution is greater than 2.8 A.  
     
     
         4 . The crystal of  claim 2  wherein the resolution is greater than 1.5 A.  
     
     
         5 . The crystal of  claim 2  in which the ligand comprises boron.  
     
     
         6 . The crystal of  claim 2 , in which the ligand comprises a furan moiety.  
     
     
         7 . The crystal of  claim 2 , in which the ligand comprises autoinducer-2.  
     
     
         8 . The crystal of  claim 7  in which the ligand has the chemical formula:  
       
         
           
           
               
               
           
         
       
     
     
         9 . A method of using the crystal of  claim 1  to identify whether a ligand binds to LuxP, comprising 
 obtaining the atomic coordinates in the crystal of at least a selected portion of LuxP;    using the atomic coordinates to model the selected portion;    identifying a potential ligand; and    docking the potential ligand to the selected portion of LuxP.    
     
     
         10 . The method of  claim 9 , wherein the selected portion comprises an amino acid residue selected from the group consisting of Trp 82, Gln 77, Ser 79, Asp 267, Thr 266, Trp 289, Arg 310, Arg 215, and Asn 159 according to Table 1.  
     
     
         11 . The method of  claim 9  in which information regarding the selected portion is stored on a computer.  
     
     
         12 . The method of  claim 9  in which a computer is used for the identifying of the potential ligand or the docking of the potential ligand to the binding site, or both.  
     
     
         13 . The method of  claim 9 , further comprising obtaining a sample of the potential ligand and contacting the sample with a prokaryotic cell.  
     
     
         14 - 17 . (canceled)