The present invention provides the structure of the enzyme
4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) synthase, a member of
the cytidyltransferase family of enzymes from Escherichia coli. CDP-ME is
a critical intermediate in the mevalonate-independent pathway for
isoprenoid biosynthesis in a number of prokaryotic organisms, in algae,
in the plastids of plants, and in the malaria parasite. Since vertebrates
synthesize isoprenoid precursors using a mevalonate pathway, CDP-ME
synthase and other enzymes of the mevalonate-independent pathway for
isoprenoid production represent attractive targets for the
structure-based design of selective antibacterial, herbicidal, and
antimalarial drugs. Accordingly, the present invention provides methods
for screening for compounds that inhibit enzymes of the
mevalonate-independent pathway and pharmaceutical compositions and
antibacterial formulations thereof. Further provided are methods of
inhibiting the enzymes of the pathway and bacterial terpenoid synthesis
and methods for treating a subject suffering from a bacterial infection.