Novel gtp cyclohydrolase type ib

Abstract

This invention relates to a novel, bacterial GTP Cyclohydrolase Type IB enzyme, and the crystal structure thereof.

1 . A computer-readable medium having GCYH-IB crystal structure information stored thereon. 
     
     
         2 . A computer-readable medium having GCYH-IB.Mn 2+  crystal structure information stored thereon. 
     
     
         3 . A computer-based method for the analysis of the interaction of a ligand with GCYH-IB, which comprises: providing the GCYH-IB structure of  FIG. 2A  and  FIG. 3A , providing the GCYH-IB active site structure of Table 10, said Table 10 being optionally varied by a rmsd of less than 1.5A, or selected co-ordinates thereof; providing a ligand structure to be fitted to said GCYH-IB structure or selected co-ordinates thereof; and fitting the ligand structure to said GCYH-IB structure, wherein said ligand structure is fitted to at least one atom from the amino acids in the group consisting of Glu150, Arg198, His246, Ser61, Arg62, His59, Glu216, Glu243, His248, Lys197, Cys147, Glu201, His259, Gln161, Ile245, Leu96, Val204, Cys149, Phe214, Asn241, Lys151, Ile153, Glu152, Pro148, Lys56, Arg220, Met60, Gly57, Thr58, Val215, Ser150, Thr205, Val21, Ala252, Ty251 and Gly22. 
     
     
         4 . The method of  claim 3  wherein said ligand is fitted to atom Zn258 of Table 10. 
     
     
         5 . The method of  claim 3  wherein said ligand is fitted to one or more atoms selected from the ligand molecule ACY259 of Table 10. 
     
     
         6 . The method of  claim 3 , wherein the GCYH-IB structure is of Table 10 optionally varied by a rmsd of less than 1.5 A, or selected coordinates thereof. 
     
     
         7 . The method of  claim 6  wherein the GCYH-IB structure is of Table 10 optionally varied by a rmsd of less than 0.5 A, or selected coordinates thereof. 
     
     
         8 . A computer-based method for the analysis of the interaction of a ligand with GCYH-IB.Mn 2+ , which comprises: providing the GCYH-IB.Mn 2+  active site structure of Table 11, said Table 11 being optionally varied by a rmsd of less than 1.5A, or selected co-ordinates thereof; providing a ligand structure to be fitted to said or GCYH-IB.Mn 2+  structure or selected co-ordinates thereof; and fitting the ligand structure to said GCYH-IB.Mn 2+  structure, wherein said ligand structure is fitted to at least one atom from the amino acids in the group consisting of Glu150, Arg198, His246, Ser61, Arg62, His 59, Glu216, Glu243, His248, Lys197, Cys147, Glu201, His259, Gln161, Ile245, Leu96, Val204, Cys149, Phe214, Asn241, Lys151, Ile153, Glu152, Pro148, Lys56, Arg220, Met60, Gly57, Thr58, Val215, Ser150, Thr205, Val21, Ala252, Ty251 and Gly22. 
     
     
         9 . The method of  claim 8  wherein said ligand is fitted to atom Mn258 of Table 11. 
     
     
         10 . The method of  claim 8  wherein said ligand is fitted to one or more atom selected from the ligand molecule AZI261 of Table 11. 
     
     
         11 . The method of  claim 8 , wherein the GCYH-IB.Mn 2+  structure is of Table 11 optionally varied by a rmsd of less than 1.5 A, or selected coordinates thereof. 
     
     
         12 . The method of  claim 11  wherein the GCYH-IB.Mn 2+  structure is of Table 11 optionally varied by a rmsd of less than 0.5 A, or selected coordinates thereof. 
     
     
         13 . A method of providing data for generating structures and/or performing optimisation of compounds which interact with GCYH-IB or GCYH-IB.Mn 2+ , or complexes of GCYH-IB or GCYH-IB.Mn 2+  with ligands, the method comprising:
 (i) establishing communication with a remote device containing computer-readable data comprising the structure of Table 10 or Table 11 optionally varied by a rmsd of less than 1.5A or selected co-ordinates thereof; and 
 (ii) receiving said computer-readable data from said remote device. 
 
     
     
         14 . The method of  claim 13  which further comprises performing the computer-based method of  claim 3 .