Patent ID: 8639486

Claim:
A method for identifying a candidate inhibitor that preferentially binds to Staphylococcus aureus N-Succinyl-L,L-DAP Desuccinylase (DapE) or a homologue or active fragment thereof in the open conformation, comprising: obtaining the structure coordinates of amino acids of DapE or homologue or active fragment thereof wherein the structure coordinates include the binding site of DapE or homologue or active fragment thereof comprises amino acid residues Glu-150, Ser-151, His-180, Gly-181, Glu-182, Lys-183, Arg-214, Asn-216, His-269, Arg-350, His-384, Tyr-385, Val-386, Asp-387, Lys-388, Thr-412, Gly-416, and His-440 of SEQ ID NO:2; generating a three-dimensional model of DapE or homologue or active fragment thereof using the structure coordinates of the amino acids from DapE in closed and open conformations, wherein the model comprises a root mean square deviation from backbone atoms of said amino acids of not more than ±1.0 Å; determining the binding site of DapE or homologue thereof in the closed confirmation from the three-dimensional model, and separately determining the binding site of DapE or homologue thereof in the open confirmation; and performing a computer fitting analysis to identify the candidate inhibitor that interacts with the binding site of DapE in the open confirmation but does not interact with the binding site of DapE in the closed configuration, and prevents interaction of the DapE lid domain with the DapE catalytic domain, wherein the interface of the catalytic domain and the lid domain comprises amino acid residues Glu-150, Ser-151, His-180, Gly-181, Glu-182, Lys-183, Arg-214, Asn-216, His-269, Arg-350, His-384, Tyr-385, Val-386, Asp-387, Lys-388, Thr-412, Gly-416, and His-440 of SEQ ID NO:2.