This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research proposed is designed to provide the structural basis for the activity of type III pantothenate kinases - also known as CoaX - in the biosynthesis of Coenzyme A in CDC/NIAID category A priority pathogens. Pantothenate kinase is responsible for the first committed step in the biosynthesis of Coenzyme A, catalyzing the phosphorylation of pantothenate to 4 -phosphopantothenate. The CoaX protein in the Priority Pathogen Bacillus anthracis will be characterized structurally. A class of pantothenate analogs known as pantothenamides has demonstrated antimetabolic activity against type I and II pantothenate kinases (found in Escherichia coli and Staphylococcus aureus, respectively), thus implicating CoaX as a target for therapeutic intervention. The data generated by the experiments proposed in this research plan will serve as structural and biochemical bases for evaluating type III PanK as a viable drug target. In addition, the structural information gained will be used in a bioinformatics approach to help evaluate the relationships between CoaX and other proteins within the Protein Kinase superfamil
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