Nonphosphate inhibitors of IspE protein, a kinase in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antirnalarial therapy

IspE kinase inhibitors. The first inhibitors for the kinase IspE, an enzyme of the non-mevalonate pathway, are presented. The nonphosphate based inhibitors avoid binding to the ATP site but instead occupy the substrate site and a small, newly detected hydrophobic subpocket at the active site of IspE. With appropriate filling of this pocket, competitive inhibition constants K ic in the upper nanomolar range are measured. (Figure Presented) © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.