IspD

IspD, also known as 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase, is an enzyme in the non-mevalonate (MEP) pathway of isoprenoid biosynthesis found in many bacteria, plastids of plants, and some parasites. It catalyzes the cytidylylation of 2-C-methyl-D-erythritol 4-phosphate (MEP) with cytidine triphosphate (CTP) to form 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDP-ME) and inorganic pyrophosphate (PPi). The reaction typically requires a divalent metal ion, such as Mg2+. IspD generally functions as a dimer and is located in the cytosol of cells.

In the MEP pathway, IspD operates after IspC (DXP reductoisomerase) and before IspE (CDP-ME kinase). The product CDP-ME is subsequently phosphorylated by IspE to form CDP-ME 2-phosphate, which continues through the pathway toward the production of the universal isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate.

Distribution and significance vary by organism, but IspD is widely conserved among bacteria and within the plastids of plants and some protozoa. The enzyme is essential for growth in many bacterial species and is absent in humans, making the IspD step an attractive target for antibacterial and antiparasitic drug development. Structural studies, including X-ray crystallography, have revealed conserved active-site motifs and aided efforts in structure-based inhibitor design. Research continues to explore selective inhibitors that disrupt the MEP pathway while minimizing effects on host metabolism.