InterPro domain: IPR034683

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) catalyses the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP) in the deoxyxylulose pathway of isopentenyl diphosphate (IPP) biosynthesis [ 1 ]. This mevalonate independent pathway that utilizes pyruvate and glyceraldehydes 3-phosphate as starting materials for production of IPP occurs in a variety of bacteria, archaea and plant cells, but is absent in mammals. The isoprenoid pathway is a well known target for anti-infective drug development [ 2 , 3 ]. In about twenty percent of bacterial genomes, this protein occurs as IspDF, a bifunctional fusion protein.

Ribitol-5-phosphate cytidylyltransferase (TarI) is required for the synthesis of activated ribitol via the wall teichoic acid biosynthesis pathway. The enzyme catalyzes the transfer of the cytidylyl group of CTP to D-ribitol 5-phosphate to form CDP-ribitol [ 4 ].

The human IspD (known as D-ribitol-5-phosphate cytidylyltransferase or isoprenoid synthase domain-containing protein) shows a canonical N-terminal cytidyltransferase domain linked to a C-terminal domain that is absent in cytidyltransferase homologues. It has cytidyltransferase activity toward pentose phosphates, including ribulose 5-phosphate, ribose 5-phosphate, and ribitol 5-phosphate. It has benn implicated in dystroglycan O-mannosylation [ 5 , 6 ].

This family consists of cytidylyltransferases IspD and TarI.

1. Biosynthesis of terpenoids: 4-diphosphocytidyl-2C-methyl-D-erythritol synthase of Arabidopsis thaliana. Proc. Natl. Acad. Sci. U.S.A. 97, 6451-6
2. Nonmevalonate terpene biosynthesis enzymes as antiinfective drug targets: substrate synthesis and high-throughput screening methods. J. Org. Chem. 71, 8824-34
3. Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development. J. Bacteriol. 189, 8922-7
4. Synthesis of CDP-activated ribitol for teichoic acid precursors in Streptococcus pneumoniae. J. Bacteriol. 191, 1200-10
5. Human ISPD Is a Cytidyltransferase Required for Dystroglycan O-Mannosylation. Chem. Biol. 22, 1643-52
6. ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto α-dystroglycan. Nat Commun 7, 11534