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72  structures 5944  species 2  interactions 7171  sequences 30  architectures

Family: IspD (PF01128)

Summary: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase

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This is the Wikipedia entry entitled "2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase". More...

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Edit Wikipedia article

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
EC number2.7.7.60
CAS number251990-59-7
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
PDB 1w77 EBI.jpg
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) from Arabidopsis thaliana
Pfam clanCL0110

In enzymology, a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (EC is an enzyme that catalyzes the chemical reaction:

2-C-methyl-D-erythritol 4-phosphate + CTP diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol

Thus, the two substrates of this enzyme are CTP and 2-C-methyl-D-erythritol 4-phosphate, whereas its two products are diphosphate and 4-diphosphocytidyl-2-C-methylerythritol.

This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases).

This enzyme participates in isoprenoid biosynthesis and stenvenosim. It catalyzes the third step of the MEP pathway; the formation of CDP-ME (4-diphosphocytidyl-2C-methyl-D-erythritol) from CTP and MEP (2C-methyl-D-erythritol 4-phosphate).[1] The isoprenoid pathway is a well known target for anti-infective drug development.[2][3]


The systematic name of this enzyme class is CTP:2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase. This enzyme is also called:

  • MEP cytidylyltransferase
  • CDP-ME synthetase

It is normally abbreviated IspD. It is also referenced by the open reading frame YgbP.

Structural studies

The crystal structure of the E. coli 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 1I52, 1INI & 1INJ, reported by Richard et al. (2001), was the first one for an enzyme involved in the MEP pathway.

As of February 2010, 13 other structures have been solved for this class of enzymes, with PDB accession codes 1H3M, 1VGT, 1VGU, 1VGZ, 1VPA, 1VGW, 1W55, 1W57, 1W77,2PX7, 2VSI, 3F1C and 2VSH.


  1. ^ Rohdich F, Wungsintaweekul J, Eisenreich W, Richter G, Schuhr CA, Hecht S, Zenk MH, Bacher A (June 2000). "Biosynthesis of terpenoids: 4-diphosphocytidyl-2C-methyl-D-erythritol synthase of Arabidopsis thaliana". Proceedings of the National Academy of Sciences of the United States of America. 97 (12): 6451–6. doi:10.1073/pnas.97.12.6451. PMC 18623. PMID 10841550.
  2. ^ Illarionova V, Kaiser J, Ostrozhenkova E, Bacher A, Fischer M, Eisenreich W, Rohdich F (November 2006). "Nonmevalonate terpene biosynthesis enzymes as antiinfective drug targets: substrate synthesis and high-throughput screening methods". J. Org. Chem. 71 (23): 8824–34. doi:10.1021/jo061466o. PMID 17081012.
  3. ^ Eoh H, Brown AC, Buetow L, Hunter WN, Parish T, Kaur D, Brennan PJ, Crick DC (December 2007). "Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development". J. Bacteriol. 189 (24): 8922–7. doi:10.1128/JB.00925-07. PMC 2168624. PMID 17921290.

Further reading

This article incorporates text from the public domain Pfam and InterPro: IPR001228

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Provide feedback

Members of this family are enzymes which catalyse the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from cytidine triphosphate and 2-C-methyl-D-erythritol 4-phosphate (MEP) [1].

Literature references

  1. Rohdich F, Wungsintaweekul J, Fellermeier M, Sagner S, Herz S, Kis K, Eisenreich W, Bacher A, Zenk MH;, Proc Natl Acad Sci U S A. 1999;96:11758-11763.: Cytidine 5'-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol. PUBMED:10518523 EPMC:10518523

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR034683

This family consists of cytidylyltransferases IspD and TarI.

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 [PUBMED:10841550]. 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 [PUBMED:17081012, PUBMED:17921290]. 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 [PUBMED:19074383].

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 [PUBMED:26687144, PUBMED:27194101].

Gene Ontology

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Domain organisation

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Seed source: Prosite
Previous IDs: UPF0007;
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A , Eberhardt R
Number in seed: 6
Number in full: 7171
Average length of the domain: 217.90 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 77.81 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.3 20.3
Noise cut-off 20.2 20.2
Model length: 221
Family (HMM) version: 20
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YgbB IspD


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IspD domain has been found. There are 72 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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