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

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
Identifiers
EC no.	2.7.7.60
CAS no.	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
Search PMC articles PubMed articles NCBI proteins

IspD
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) from Arabidopsis thaliana
Identifiers
Symbol	IspD
Pfam	PF01128
Pfam clan	CL0110
InterPro	IPR001228
PROSITE	PDOC00997
SCOP2	1inj / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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 ${\displaystyle \rightleftharpoons }$ diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol

• 
  2-C-methylerythritol 4-phosphate
• 
  Cytidine triphosphate
• 
  4-diphosphocytidyl-2-C-methylerythritol (CDP-ME)

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. 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. Bibcode:2000PNAS...97.6451R. 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

• 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. S2CID   8494543.
• 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.

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