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

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Short description: Class of enzymes
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
Identifiers
EC number2.7.7.60
CAS number251990-59-7
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
IspD
PDB 1w77 EBI.jpg
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) from Arabidopsis thaliana
Identifiers
SymbolIspD
PfamPF01128
Pfam clanCL0110
InterProIPR001228
PROSITEPDOC00997
SCOP21inj / SCOPe / SUPFAM

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 [math]\displaystyle{ \rightleftharpoons }[/math] 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

  1. "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. June 2000. doi:10.1073/pnas.97.12.6451. PMID 10841550. Bibcode2000PNAS...97.6451R. 
  2. "Nonmevalonate terpene biosynthesis enzymes as antiinfective drug targets: substrate synthesis and high-throughput screening methods". J. Org. Chem. 71 (23): 8824–34. November 2006. doi:10.1021/jo061466o. PMID 17081012. 
  3. "Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development". J. Bacteriol. 189 (24): 8922–7. December 2007. doi:10.1128/JB.00925-07. PMID 17921290. 

Further reading

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