2.0 2012-05-31 14:26:32 -0600 2015-09-17 15:42:09 -0600 ECMDB20083 M2MDB000931 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol 4-(cytidine 5'-diphospho)-2-c-methyl-D-erythritol is a member of the chemical class known as Pyrimidine Ribonucleoside Diphosphates. These are pyrimidine ribobucleotides with diphosphate group linked to the ribose moiety. CDP-ME is an intermediate in the mevalonate-independent pathway for isoprenoid biosynthesis in a number of prokaryotic organisms, algae, the plant plastids and the malaria parasite. (PMID 11427897) In the MEP pathway, 4-diphosphocytidyl-2-C-methyl-D-erythritol is formed from 2-C-methyl-D-erythritol 4-phosphate (MEP) and CTP in a reaction catalyzed by a 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (IspD). (PMID 17921290) Diphosphocytidyl-methylerythritol (DPCME) synthetase is involved in the mevalonate-independent pathway of isoprenoid biosynthesis, where it catalyses the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from 2-C-methyl-D-erythritol 4-phosphate and CTP. (PMID 11468415) 4-CDP-2-C-Methyl-D-erythritol 4-DIPHOSPHOCYTIDYL-2-C-METHYL-D-ERYTHRITOL 4-Diphosphocytidyl-2-C-methylerythritol 4-Diphosphocytidyl-2C-methyl-D-erythritol CDM CDP-ME CDP-Methyl-D-erythritol PPCytMeEry C14H23N3O14P2 519.294 519.066623588 [({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2-hydroxy-4-imino-1,4-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy][(2R,3S)-2,3,4-trihydroxy-3-methylbutoxy]phosphinic acid 4-cdp-2-C-methyl-D-erythritol [H][C@@](O)(COP(O)(=O)OP([O-])(=O)OC[C@@]1([H])O[C@@]([H])(N2C=CC(=N)N=C2[O-])[C@]([H])(O)[C@]1([H])O)[C@@](C)(O)CO InChI=1S/C14H25N3O14P2/c1-14(23,6-18)8(19)5-29-33(26,27)31-32(24,25)28-4-7-10(20)11(21)12(30-7)17-3-2-9(15)16-13(17)22/h2-3,7-8,10-12,18-21,23H,4-6H2,1H3,(H,24,25)(H,26,27)(H2,15,16,22)/p-2/t7-,8-,10-,11-,12-,14+/m1/s1 YFAUKWZNPVBCFF-XHIBXCGHSA-L Cytosol logp -1.78 ALOGPS logs -1.69 ALOGPS solubility 1.08e+01 g/l ALOGPS logp -5.3 ChemAxon pka_strongest_acidic 1.77 ChemAxon pka_strongest_basic 3.34 ChemAxon iupac [({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2-hydroxy-4-imino-1,4-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy][(2R,3S)-2,3,4-trihydroxy-3-methylbutoxy]phosphinic acid ChemAxon average_mass 519.294 ChemAxon mono_mass 519.066623588 ChemAxon smiles [H][C@@](O)(COP(O)(=O)OP([O-])(=O)OC[C@@]1([H])O[C@@]([H])(N2C=CC(=N)N=C2[O-])[C@]([H])(O)[C@]1([H])O)[C@@](C)(O)CO ChemAxon formula C14H23N3O14P2 ChemAxon inchi InChI=1S/C14H25N3O14P2/c1-14(23,6-18)8(19)5-29-33(26,27)31-32(24,25)28-4-7-10(20)11(21)12(30-7)17-3-2-9(15)16-13(17)22/h2-3,7-8,10-12,18-21,23H,4-6H2,1H3,(H,24,25)(H,26,27)(H2,15,16,22)/p-2/t7-,8-,10-,11-,12-,14+/m1/s1 ChemAxon inchikey YFAUKWZNPVBCFF-XHIBXCGHSA-L ChemAxon polar_surface_area 272.35 ChemAxon refractivity 115.04 ChemAxon polarizability 44.23 ChemAxon rotatable_bond_count 11 ChemAxon acceptor_count 14 ChemAxon donor_count 9 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Terpenoid backbone biosynthesis ec00900 Metabolic pathways eco01100 Secondary metabolites: isoprenoid biosynthesis (nonmevalonate pathway) The biosynthesis of isoprenoids starts with a D-glyceraldehyde 3-phosphate interacting with a hydrogen ion through a 1-deoxyxylulose-5-phosphate synthase resulting in a carbon dioxide and 1-Deoxy-D-xylulose. The latter compound then interacts with a hydrogen ion through a NADPH driven 1-deoxy-D-xylulose 5-phosphate reductoisomerase resulting in a NADP and a 2-C-methyl-D-erythritol 4-phosphate. The latter compound then interacts with a cytidine triphosphate and a hydrogen ion through a 4-diphosphocytidyl-2C-methyl-D-erythritol synthase resulting in a pyrophosphate and a 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound is then phosphorylated through an ATP driven 4-diphosphocytidyl-2-C-methylerythritol kinase resulting in a release of an ADP, a hydrogen ion and a 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound then interacts with a 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase resulting in the release of a 2-C-methyl-D-erythritol-2,4-cyclodiphosphate resulting in the release of a cytidine monophosphate and 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. The latter compound then interacts with a reduced flavodoxin through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase resulting in the release of a water molecule, a hydrogen ion, an oxidized flavodoxin and a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. The compound 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate can interact with an NADPH,a hydrogen ion through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase resulting in a NADP, a water molecule and either a Dimethylallylpyrophosphate or a Isopentenyl pyrophosphate. These two last compounds can be are isomers that can be produced through a isopentenyl diphosphate isomerase.and then get incorporated into the methylerythritol phosphate and polyisoprenoid biosynthesis pathway PW000975 Metabolic Secondary metabolites: methylerythritol phosphate and polyisoprenoid biosynthesis The biosynthesis of isoprenoids starts with a D-glyceraldehyde 3-phosphate interacting with a hydrogen ion through a 1-deoxyxylulose-5-phosphate synthase resulting in a carbon dioxide and 1-Deoxy-D-xylulose. The latter compound then interacts with a hydrogen ion through a NADPH driven 1-deoxy-D-xylulose 5-phosphate reductoisomerase resulting in a NADP and a 2-C-methyl-D-erythritol 4-phosphate. The latter compound then interacts with a cytidine triphosphate and a hydrogen ion through a 4-diphosphocytidyl-2C-methyl-D-erythritol synthase resulting in a pyrophosphate and a 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound is then phosphorylated through an ATP driven 4-diphosphocytidyl-2-C-methylerythritol kinase resulting in a release of an ADP, a hydrogen ion and a 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound then interacts with a 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase resulting in the release of a 2-C-methyl-D-erythritol-2,4-cyclodiphosphate resulting in the release of a cytidine monophosphate and 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. The latter compound then interacts with a reduced flavodoxin through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase resulting in the release of a water molecule, a hydrogen ion, an oxidized flavodoxin and a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. The compound 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate can interact with an NADPH,a hydrogen ion through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase resulting in a NADP, a water molecule and either a Dimethylallylpyrophosphate or a Isopentenyl pyrophosphate. These two last compounds can be are isomers that can be produced through a isopentenyl diphosphate isomerase. Dimethylallylpyrophosphate interacts with the isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in a pyrophosphate and a geranyl--PP. The latter compound interacts with a Isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in the release of a pyrophosphate and a farnesyl pyrophosphate. The latter compound interacts with isopentenyl pyrophosphate either through a undecaprenyl diphosphate synthase resulting in a release of a pyrophosphate and a di-trans,octa-cis-undecaprenyl diphosphate or through a octaprenyl diphosphate synthase resulting in a pyrophosphate and an octaprenyl diphosphate PW000958 Metabolic methylerythritol phosphate pathway NONMEVIPP-PWY Specdb::MsMs 29744 Specdb::MsMs 29745 Specdb::MsMs 29746 Specdb::MsMs 36302 Specdb::MsMs 36303 Specdb::MsMs 36304 Specdb::MsMs 3608116 Specdb::MsMs 3608117 Specdb::MsMs 3608118 Specdb::MsMs 3608119 Specdb::MsMs 3608120 Specdb::MsMs 3608121 443199 391471 C11435 16578 4-CYTIDINE-5-DIPHOSPHO-2-C CDM Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Eoh, H., Brown, A. C., Buetow, L., Hunter, W. N., Parish, T., Kaur, D., Brennan, P. J., Crick, D. C. (2007). "Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development." J Bacteriol 189:8922-8927. 17921290 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase P62615 ISPE_ECOLI ispE http://ecmdb.ca/proteins/P62615.xml 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Q46893 ISPD_ECOLI ispD http://ecmdb.ca/proteins/Q46893.xml 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Adenosine triphosphate <> 2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + ADP + Hydrogen ion R05634 2.7.1.148-RXN 2-C-Methyl-D-erythritol-4-phosphate + Cytidine triphosphate + Hydrogen ion <> 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Pyrophosphate R05633 2.7.7.60-RXN 2-C-Methyl-D-erythritol-4-phosphate + Cytidine triphosphate <> 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Pyrophosphate R05633 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Adenosine triphosphate <> 2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + ADP R05634 2.7.1.148-RXN 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Adenosine triphosphate > Hydrogen ion + 2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + ADP 2.7.1.148-RXN Hydrogen ion + 2-C-Methyl-D-erythritol-4-phosphate + Cytidine triphosphate > 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Pyrophosphate 2.7.7.60-RXN Cytidine triphosphate + 2-C-methyl-D-erythritol 4-phosphate > Pyrophosphate + 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol Adenosine triphosphate + 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol > ADP + 2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol 2-C-methyl-D-erythritol 4-phosphate + Cytidine triphosphate + Hydrogen ion > Pyrophosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol PW_R003689 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Adenosine triphosphate + 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol > Adenosine diphosphate + Hydrogen ion + 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + ADP + 2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol PW_R003690 4 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Adenosine triphosphate <>2 2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + ADP + Hydrogen ion 4 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol + Adenosine triphosphate <>2 2-Phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol + ADP + Hydrogen ion