Rhea - reaction knowledgebase

Enzymes

UniProtKB ^help_outline	31,637 proteins
Enzyme class ^help_outline	EC 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
GO Molecular Function ^help_outline	GO:0050518 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity

Reaction participants Show >> << Hide

Name ^help_outline 2-C-methyl-D-erythritol 4-phosphate Identifier CHEBI:58262 Charge -2 Formula C5H11O7P InChIKey^help_outline XMWHRVNVKDKBRG-UHNVWZDZSA-L SMILES^help_outline C[C@](O)(CO)[C@H](O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline CTP Identifier CHEBI:37563 (Beilstein: 4732530) ^help_outline Charge -4 Formula C9H12N3O14P3 InChIKey^help_outline PCDQPRRSZKQHHS-XVFCMESISA-J SMILES^help_outline Nc1ccn([C@@H]2O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]2O)c(=O)n1 2D coordinates Mol file for the small molecule Search links Involved in 81 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline H⁺ Identifier CHEBI:15378 Charge 1 Formula H InChIKey^help_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILES^help_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline 4-CDP-2-C-methyl-D-erythritol Identifier CHEBI:57823 (Beilstein: 9372838) ^help_outline Charge -2 Formula C14H23N3O14P2 InChIKey^help_outline YFAUKWZNPVBCFF-XHIBXCGHSA-L SMILES^help_outline C[C@](O)(CO)[C@H](O)COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1ccc(N)nc1=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline diphosphate Identifier CHEBI:33019 (Beilstein: 185088) ^help_outline Charge -3 Formula HO7P2 InChIKey^help_outline XPPKVPWEQAFLFU-UHFFFAOYSA-K SMILES^help_outline OP([O-])(=O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,129 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:13429	RHEA:13430	RHEA:13431	RHEA:13432
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	31,637 proteins	1 proteins
EC numbers ^help_outline	2.7.7.60
Gene Ontology ^help_outline	GO:0050518
KEGG ^help_outline				R05633
MetaCyc ^help_outline				2.7.7.60-RXN
EcoCyc ^help_outline				2.7.7.60-RXN

Publications

Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development.

Eoh H., Brown A.C., Buetow L., Hunter W.N., Parish T., Kaur D., Brennan P.J., Crick D.C.

Mycobacterium tuberculosis utilizes the methylerythritol phosphate (MEP) pathway for biosynthesis of isopentenyl diphosphate and its isomer, dimethylallyl diphosphate, precursors of all isoprenoid compounds. This pathway is of interest as a source of new drug targets, as it is absent from humans a ... >> More

Mycobacterium tuberculosis utilizes the methylerythritol phosphate (MEP) pathway for biosynthesis of isopentenyl diphosphate and its isomer, dimethylallyl diphosphate, precursors of all isoprenoid compounds. This pathway is of interest as a source of new drug targets, as it is absent from humans and disruption of the responsible genes has shown a lethal phenotype for Escherichia coli. 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). In the present work, we demonstrate that Rv3582c is essential for M. tuberculosis: Rv3582c has been cloned and expressed, and the encoded protein has been purified. The purified M. tuberculosis IspD protein was capable of catalyzing the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol in the presence of MEP and CTP. The enzyme was active over a broad pH range (pH 6.0 to 9.0), with peak activity at pH 8.0. The activity was absolutely dependent upon divalent cations, with 20 mM Mg2+ being optimal, and replacement of CTP with other nucleotide 5'-triphosphates did not support activity. Under the conditions tested, M. tuberculosis IspD had Km values of 58.5 microM for MEP and 53.2 microM for CTP. Calculated kcat and kcat/Km values were 0.72 min(-1) and 12.3 mM(-1) min(-1) for MEP and 1.0 min(-1) and 18.8 mM(-1) min(-1) for CTP, respectively. << Less

J Bacteriol 189:8922-8927(2007) [PubMed] [EuropePMC]
Biosynthesis of isoprenoids: characterization of a functionally active recombinant 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) from Mycobacterium tuberculosis H37Rv.

Shi W., Feng J., Zhang M., Lai X., Xu S., Zhang X., Wang H.

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be one of the leading infectious diseases to humans. It is urgent to discover novel drug targets for the development of antitubercular agents. The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has been ... >> More

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be one of the leading infectious diseases to humans. It is urgent to discover novel drug targets for the development of antitubercular agents. The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has been considered as an attractive target for the discovery of novel antibiotics for its essentiality in bacteria and absence in mammals. MEP cytidyltransferase (IspD), the third-step enzyme of the pathway, catalyzes MEP and CTP to form 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) and PPi. In the work, ispD gene from M. tuberculosis H37Rv (MtIspD) was cloned and expressed. With N-terminal fusion of a histidine-tagged sequence, MtIspD could be purified to homogeneity by one-step nickel affinity chromatography. MtIspD exists as a homodimer with an apparent molecular mass of 52 kDa. Enzyme property analysis revealed that MtIspD has high specificity for pyrimidine bases and narrow divalent cation requirements, with maximal activity found in the presence of CTP and Mg(2+). The turnover number of MtIspD is 3.4 s(-1). The Km for MEP and CTP are 43 and 92 muM, respectively. Furthermore, MtIspD shows thermal instable above 50 degrees C. Circular dichroism spectra revealed that the alteration of tertiary conformation is closely related with sharp loss of enzyme activity at higher temperature. This study is expected to help better understand the features of IspD and provide useful information for the development of novel antibiotics to treat M. tuberculosis. << Less

J Biochem Mol Biol 40:911-920(2007) [PubMed] [EuropePMC]

RHEA:13429 2-C-methyl-D-erythritol 4-phosphate + CTP + H(+) = 4-CDP-2-C-methyl-D-erythritol + diphosphate

Enzymes

Reaction participants Show >> << Hide

Cross-references

Publications

Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development.

Biosynthesis of isoprenoids: characterization of a functionally active recombinant 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) from Mycobacterium tuberculosis H37Rv.