Novel histidine kinase

Abstract

The invention provides histidine kinase polypeptides and DNA (RNA) encoding histidine kinase polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing histidine kinase polypeptides to screen for antibacterial compounds.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of: 
 (a) a polynucleotide having at least a 70% identity to a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:2;    (b) a polynucleotide having at least a 70% identity to a polynucleotide encoding the same mature polypeptide expressed by the histidine kinase gene contained in the  Streptococcus pneumoniae  of the deposited strain;    (c) a polynucleotide encoding a polypeptide comprising an amino acid sequence which is at least 70% identical to the amino acid sequence of SEQ ID NO:2;    (d) a polynucleotide which is complementary to the polynucleotide of (a), (b) or (c); and    (e) a polynucleotide comprising at least 15 sequential bases of the polynucleotide of (a), (b) or (c).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of  claim 2  comprising the nucleic acid sequence set forth in SEQ ID NO:1.  
     
     
         5 . The polynucleotide of  claim 2  comprising nucleotide 1 to 1050 set forth in SEQ ID NO:1.  
     
     
         6 . The polynucleotide of  claim 2  which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         7 . A vector comprising the polynucleotide of  claim 1 .  
     
     
         8 . A host cell comprising the vector of  claim 7 .  
     
     
         9 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 8  a polypeptide encoded by said DNA.  
     
     
         10 . A process for producing a histidine kinase polypeptide or fragment comprising culturing a host of  claim 8  under conditions sufficient for the production of said polypeptide or fragment.  
     
     
         11 . A polypeptide comprising an amino acid sequence which is at least 70% identical to the amino acid sequence of SEQ ID NO:2.  
     
     
         12 . A polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:2.  
     
     
         13 . An antibody against the polypeptide of  claim 11 .  
     
     
         14 . An antagonist which inhibits the activity or expression of the polypeptide of  claim 11 .  
     
     
         15 . A method for the treatment of an individual in need of histidine kinase polypeptide comprising: administering to the individual a therapeutically effective amount of the polypeptide of  claim 11 .  
     
     
         16 . A method for the treatment of an individual having need to inhibit histidine kinase polypeptide comprising: administering to the individual a therapeutically effective amount of the antagonist of  claim 14 .  
     
     
         17 . A process for diagnosing a disease related to expression or activity of the polypeptide of  claim 11  in an individual comprising: 
 (a) determining a nucleic acid sequence encoding said polypeptide, and/or  
 (b) analyzing for the presence or amount of said polypeptide in a sample derived from the individual.  
 
     
     
         18 . A method for identifying compounds which interact with and inhibit or activate an activity of the polypeptide of  claim 11  comprising: 
 contacting a composition comprising the polypeptide with the compound to be screened under conditions to permit interaction between the compound and the polypeptide to assess the interaction of a compound, such interaction being associated with a second component capable of providing a detectable signal in response to the interaction of the polypeptide with the compound;  
 and determining whether the compound interacts with and activates or inhibits an activity of the polypeptide by detecting the presence or absence of a signal generated from the interaction of the compound with the polypeptide.  
 
     
     
         19 . A method for inducing an immunological response in a mammal which comprises inoculating the mammal with histidine kinase polypeptide of  claim 11 , or a fragment or variant thereof, adequate to produce antibody and/or T cell immune response to protect said animal from disease.  
     
     
         20 . A method of inducing immunological response in a mammal which comprises delivering a nucleic acid vector to direct expression of histidine kinase polypeptide of  claim 11 , or fragment or a variant thereof, for expressing said histidine kinase polypeptide, or a fragment or a variant thereof in vivo in order to induce an immunological response to produce antibody and/or T cell immune response to protect said animal from disease.