Sporadic outbreaks of plague, lack of a vaccine, emergence of multidrug-resistant strains of Yersinia pestis, and its potential use in bioterrorism, call for an urgent need to develop new drugs for plague. We have used comparative metabolic pathway analysis to identify 245 drug-target candidate enzymes in Y. pestis CO92 which are non-homologous to host Homo sapiens and likely to be essential for the pathogen's survival. Further analysis revealed that 25 of these are potential choke point enzymes. As a case study, structure of a choke point enzyme, MurE ligase, was modeled and docking studies performed against a library of compounds leading to identification of a potential inhibitor. This approach enables rapid potential drug-target identification, thereby facilitating search for new antimicrobials.
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