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49  structures 3924  species 3  interactions 4492  sequences 13  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
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 / EGO
IspD
PDB 1w77 EBI.jpg
2c-methyl-d-erythritol 4-phosphate cytidylyltransferase (ispd) from arabidopsis thaliana
Identifiers
Symbol IspD
Pfam PF01128
Pfam clan CL0110
InterPro IPR001228
PROSITE PDOC00997
SCOP 1inj
SUPERFAMILY 1inj

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 \rightleftharpoons 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-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol.

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

This enzyme participates in biosynthesis of steroids. It catalyzes the third step of the deoxyxylulose-5-phosphate pathway (DXP) of isoprenoid biosynthesis; the formation of 4-diphosphocytidyl-2C-methyl-D-erythritol from CTP and 2C-methyl-D-erythritol 4-phosphate.[1] The isoprenoid pathway is a well known target for anti-infective drug development.[2][3]

Nomenclature[edit]

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

  • MEP cytidylyltransferas
  • CDP-ME synthetase

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

Structural studies[edit]

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[edit]

  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[edit]

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


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001228

4-diphosphocytidyl-2C-methyl-D-erythritol synthase, a bacterial ispD protein, catalyzes the third step of the deoxyxylulose-5-phosphate pathway (DXP) of isoprenoid biosynthesis; the formation of 4-diphosphocytidyl-2C-methyl-D-erythritol from CTP and 2C-methyl-D-erythritol 4-phosphate [PUBMED:10841550]. The isoprenoid pathway is a well known target for anti-infective drug development [PUBMED:17081012, PUBMED:17921290].

Gene Ontology

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Domain organisation

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Alignments

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(6)
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(4492)
Representative proteomes NCBI
(7221)
Meta
(4670)
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(339)
RP35
(640)
RP55
(817)
RP75
(957)
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  Seed
(6)
Full
(4492)
Representative proteomes NCBI
(7221)
Meta
(4670)
RP15
(339)
RP35
(640)
RP55
(817)
RP75
(957)
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  Seed
(6)
Full
(4492)
Representative proteomes NCBI
(7221)
Meta
(4670)
RP15
(339)
RP35
(640)
RP55
(817)
RP75
(957)
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Seed source: Prosite
Previous IDs: UPF0007;
Type: Family
Author: Finn RD, Bateman A, Eberhardt R
Number in seed: 6
Number in full: 4492
Average length of the domain: 220.50 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 84.34 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -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: 14
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Interactions

There are 3 interactions for this family. More...

Hexapep IspD YgbB

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 49 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 seqence.

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