Summary: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
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2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Edit Wikipedia article
| 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | |||||||||
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| Identifiers | |||||||||
| EC number | 2.7.7.60 | ||||||||
| CAS number | 251990-59-7 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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| IspD | |||||||||
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 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) from Arabidopsis thaliana | |||||||||
| Identifiers | |||||||||
| Symbol | IspD | ||||||||
| Pfam | PF01128 | ||||||||
| Pfam clan | CL0110 | ||||||||
| InterPro | IPR001228 | ||||||||
| PROSITE | PDOC00997 | ||||||||
| SCOPe | 1inj / SUPFAM | ||||||||
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In enzymology, a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (EC 2.7.7.60) 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]
Nomenclature
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.
References
- ^ 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.
- ^ 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.
- ^ 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
- Richard SB, Bowman ME, Kwiatkowski W, Kang I, Chow C, Lillo AM, Cane DE, Noel JP (2001). "Structure of 4-diphosphocytidyl-2-C- methylerythritol synthetase involved in mevalonate- independent isoprenoid biosynthesis". Nature Structural & Molecular Biology. 8 (7): 641–8. doi:10.1038/89691. PMID 11427897.
- Kuzuyama T; Takagi M; Kaneda K; Dairi T; Seto H (2000). "Formation of 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol from 2-C-methyl-D-erythritol 4-phosphate by 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, a new enzyme in the nonmevalonate pathway". Tetrahedron Lett. 41 (50): 703–706. doi:10.1016/S0040-4039(99)02143-7.
- Rohdich F, Wungsintaweekul J, Fellermeier M, et al. (1999). "Cytidine 5'-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol". Proc. Natl. Acad. Sci. USA. 96 (21): 11758–63. doi:10.1073/pnas.96.21.11758. PMC 18359. PMID 10518523.
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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
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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
| SCOOP: | CofC CTP_transf_3 DUF2064 Glyco_tranf_2_3 Glycos_transf_2 NTP_transf_3 NTP_transferase |
| Similarity to PfamA using HHSearch: | CTP_transf_3 NTP_transf_3 |
External database links
| PROSITE: | PDOC00997 |
| SCOP: | 1inj |
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
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | cytidylyltransferase activity (GO:0070567) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan GT-A (CL0110), which has the following description:
This is the GT-A clan that contains diverse glycosyltransferases that possess a Rossmann like fold [1].
The clan contains the following 52 members:
Anp1 Branch Caps_synth Cellulose_synt CgtA CHGN Chitin_synth_1 Chitin_synth_2 CofC CTP_transf_3 DUF2064 DUF273 DUF604 Fringe Galactosyl_T GlcNAc Gly_transf_sug Glyco_tranf_2_2 Glyco_tranf_2_3 Glyco_tranf_2_4 Glyco_tranf_2_5 Glyco_trans_2_3 Glyco_transf_15 Glyco_transf_21 Glyco_transf_24 Glyco_transf_25 Glyco_transf_34 Glyco_transf_43 Glyco_transf_49 Glyco_transf_6 Glyco_transf_64 Glyco_transf_7C Glyco_transf_7N Glyco_transf_8 Glyco_transf_88 Glyco_transf_92 Glycos_transf_2 GNT-I IspD Mannosyl_trans3 MGAT2 NTP_transf_3 NTP_transferase Nucleotid_trans Osmo_MPGsynth Pox_P35 RGP Rhamno_transf STELLO TcdA_TcdB UDP-g_GGTase UDPGPAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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| Seed (6) |
Full (7171) |
Representative proteomes | UniProt (32919) |
NCBI (104890) |
Meta (4670) |
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| RP15 (943) |
RP35 (3536) |
RP55 (7103) |
RP75 (12113) |
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| Jalview | |||||||||
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| PP/heatmap | 1 | ||||||||
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| Seed (6) |
Full (7171) |
Representative proteomes | UniProt (32919) |
NCBI (104890) |
Meta (4670) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (943) |
RP35 (3536) |
RP55 (7103) |
RP75 (12113) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Prosite |
| Previous IDs: | UPF0007; |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Finn RD  , Bateman A , Eberhardt R
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| 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 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 221 | ||||||||||||
| Family (HMM) version: | 20 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Structures
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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