4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE) (IspE)

4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, commonly referred to as IspE, is a critical enzyme in the methylerythritol phosphate (MEP) pathway, also known as the non-mevalonate pathway [1, 3]. This pathway is essential for the biosynthesis of isoprenoids, which are vital precursors for various cellular components in many bacteria, plants, and apicomplexan protozoa [4, 7]. IspE catalyzes the ATP-dependent phosphorylation of the 2-hydroxy group of 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDP-ME) to produce 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-MEP) [1, 5]. Because humans and other mammals utilize the alternative mevalonate pathway for isoprenoid synthesis, IspE represents a promising target for the development of selective antimicrobial and antimalarial agents with minimal host toxicity [2, 4]. Research has identified several classes of small-molecule inhibitors, including thiazine and isoxazolone derivatives, which demonstrate potent inhibition of the enzyme in pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum [2, 4]. Targeting IspE effectively disrupts the production of essential isoprenoids, leading to the cessation of pathogen growth and survival [2].

Other names

4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinaseCDP-ME kinaseCMK4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphotransferaseYchBIpk

Inhibition of 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase activity, blocking the conversion of CDP-ME to CDP-MEP and disrupting isoprenoid biosynthesis.