4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG)

4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG) is an iron–sulfur (4Fe-4S) enzyme that catalyzes the penultimate step in the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, converting 2C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) into (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate (HMBPP)[1][4][6]. This pathway is found in most bacteria, many protozoan parasites (such as malaria), and plant plastids, but not in humans, making IspG a promising target for new anti-infective agents[5]. IspG enzymes require a specific [4Fe-4S] cluster for catalytic activity and interact with electron carrier proteins such as flavodoxin or ferredoxin to receive reducing equivalents[4][6]. Structural studies reveal domain architectures adapted for catalysis and explain the basis for species-selective inhibitor design[1][2].

Other names

GcpEHMBPP synthase1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase

Enzyme inhibition (inhibitors typically block catalysis via direct interaction with the [4Fe-4S] cluster or by mimicking substrate/intermediate)[1][5]