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. Our laboratory is attempting to solve the structures of the enzymes in the mevalonate- isoprenoid pathway from prokaryotes. This pathway has been shown to be essential to pathological gram-positive cocci that are frequently associated with secondary infections from trauma or surgical wounds/appliances. Mapping the structural space of this pathway raises the possibility of a directed search for inhibitors that could provide targeted growth inhibition of the cocci without the complications of broad spectrum antibiotics. All but one of these six enzymes have been cloned, crystals obtained from three, and structures from two.
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