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

4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate
Names
IUPAC name
Cytidine 5′-(1-deoxy-2-C-methyl-2-O-phosphono-D-erythritol-1-yl dihydrogen diphosophate)
Systematic IUPAC name
O1-{[(2R,3S,4R,5R)-5-(4-Amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxyoxan-2-yl]methyl} O3-[(2R,3S)-2,4-dihydroxy-3-methyl-3-(phosphonooxy)butyl] dihydrogen diphosphate
Identifiers
3D model (JSmol)
8528909
ChEBI
ChemSpider
DrugBank
KEGG
MeSH 4-diphosphocytidyl-2C+methylerythritol+2-phosphate
  • InChI=1S/C14H26N3O17P3/c1-14(6-18,33-35(23,24)25)8(19)5-31-37(28,29)34-36(26,27)30-4-7-10(20)11(21)12(32-7)17-3-2-9(15)16-13(17)22/h2-3,7-8,10-12,18-21H,4-6H2,1H3,(H,26,27)(H,28,29)(H2,15,16,22)(H2,23,24,25)/t7-,8-,10-,11-,12-,14+/m1/s1
    Key: HTJXTKBIUVFUAR-XHIBXCGHSA-N
  • C[C@](CO)([C@@H](COP(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=CC(=NC2=O)N)O)O)O)OP(=O)(O)O
Properties
C14H26N3O17P3
Molar mass 601.29 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (or CDP-MEP, 4-diphosphocytidyl-2C methylerythritol 2-phosphate) is an intermediate in the MEP pathway of isoprenoid precursor biosynthesis.

It is formed by CDP-ME kinase (IspE) and is a substrate for 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF).

Biochemical role

CDP-MEP is an intermediate in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate. Most gram-negative bacteria, the photosynthetic cyanobacteria and green algae use only this pathway, while higher plants also use the mevalonate pathway.

The enzyme 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase uses the cofactor, adenosine triphosphate (ATP) to introduce a terminal phosphate group to the immediate precursor, 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME), giving CDP-MEP and adenosine diphosphate (ADP):

ATP +
 
2D representation of the chemical structure of 4-Diphosphocytidyl-2-C-methylerythritol.
CDP-ME
 
 
 
Rightward reaction arrow
 
 
 
ADP +
 
2D representation of the chemical structure of 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate.
CDP-MEP

The next reaction, catalyzed by 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, splits CDP-MEP into 2-C-methyl-D-erythritol 2,4-cyclic diphosphate (MEcPP) and cytidine monophosphate.

CDP-MEP
 
 
 
 
Rightward reaction arrow
 
 
 
2D representation of the chemical structure of Q27103069.
MEcPP
+
 
2D representation of the chemical structure of cytidine monophosphate .
cytidine monophosphate

References

  1. ↑ Narayanasamy P, Eoh H, Brennan PJ, Crick DC (2010). "Synthesis of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate and kinetic studies of Mycobacterium tuberculosis IspF, a potential drug target". Chem Biol. 17 (2): 117–22. doi:10.1016/j.chembiol.2010.01.013. PMC 2837070. PMID 20189102.
  2. ↑ W. Eisenreich; A. Bacher; D. Arigoni; F. Rohdich (2004). "Review Biosynthesis of isoprenoids via the non-mevalonate pathway". Cellular and Molecular Life Sciences. 61 (12): 1401–1426. doi:10.1007/s00018-004-3381-z. PMC 11138651. PMID 15197467. S2CID 24558920.
  3. ↑ Hunter, WN (2007). "The Non-mevalonate Pathway of Isoprenoid Precursor Biosynthesis". Journal of Biological Chemistry. 282 (30): 21573–21577. doi:10.1074/jbc.R700005200. PMID 17442674.
  4. ↑ Rohmer M; Rohmer, Michel (1999). "The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants". Nat Prod Rep. 16 (5): 565–574. doi:10.1039/a709175c. PMID 10584331.
  5. ↑ Vranová, Eva; Coman, Diana; Gruissem, Wilhelm (2013-04-29). "Network Analysis of the MVA and MEP Pathways for Isoprenoid Synthesis". Annual Review of Plant Biology. 64 (1): 665–700. Bibcode:2013AnRPB..64..665V. doi:10.1146/annurev-arplant-050312-120116. ISSN 1543-5008. PMID 23451776.
  6. ↑ Lüttgen H, Rohdich F, Herz S, Wungsintaweekul J, Hecht S, Schuhr CA, Fellermeier M, Sagner S, Zenk MH, Bacher A, Eisenreich W (2000). "Biosynthesis of terpenoids: YchB protein of Escherichia coli phosphorylates the 2-hydroxy group of 4-diphosphocytidyl-2C-methyl-d-erythritol". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1062–7. Bibcode:2000PNAS...97.1062L. doi:10.1073/pnas.97.3.1062. PMC 15522. PMID 10655484.
  7. ↑ Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Lüttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F (2000). "Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate to 2C-methyl-d-erythritol 2,4-cyclodiphosphate". Proc. Natl. Acad. Sci. USA. 97 (6): 2486–90. Bibcode:2000PNAS...97.2486H. doi:10.1073/pnas.040554697. PMC 15955. PMID 10694574.