Nonphosphate Inhibitors of IspE Protein, a Kinase in the Non‐Mevalonate Pathway for Isoprenoid Biosynthesis and a Potential Target for Antimalarial Therapy

Abstract

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 Kic in the upper nanomolar range are measured.