Rhea - reaction knowledgebase

Enzymes

UniProtKB ^help_outline	18,706 proteins
Enzyme class ^help_outline	EC 2.7.7.38 3-deoxy-manno-octulosonate cytidylyltransferase
GO Molecular Function ^help_outline	GO:0008690 3-deoxy-manno-octulosonate cytidylyltransferase activity

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Name ^help_outline 3-deoxy-α-D-manno-oct-2-ulosonate Identifier CHEBI:85986 Charge -1 Formula C8H13O8 InChIKey^help_outline NNLZBVFSCVTSLA-HXUQBWEZSA-M SMILES^help_outline OC[C@@H](O)[C@H]1O[C@](O)(C[C@@H](O)[C@H]1O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 4 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 83 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline CMP-3-deoxy-β-D-manno-octulosonate Identifier CHEBI:85987 Charge -2 Formula C17H24N3O15P InChIKey^help_outline YWWJKULNWGRYAS-UOVSKDHASA-L SMILES^help_outline Nc1ccn([C@@H]2O[C@H](COP([O-])(=O)O[C@]3(C[C@@H](O)[C@@H](O)[C@H](O3)[C@H](O)CO)C([O-])=O)[C@@H](O)[C@H]2O)c(=O)n1 2D coordinates Mol file for the small molecule Search links Involved in 11 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 1,146 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:23448	RHEA:23449	RHEA:23450	RHEA:23451
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	18,706 proteins
EC numbers ^help_outline	2.7.7.38
Gene Ontology ^help_outline	GO:0008690
KEGG ^help_outline				R03351
MetaCyc ^help_outline		CPM-KDOSYNTH-RXN
EcoCyc ^help_outline		CPM-KDOSYNTH-RXN

Publications

The biosynthesis of cell wall lipopolysaccharide in Escherichia coli. IV. Purification and properties of cytidine monophosphate 3-deoxy-d-manno-octulosonate synthetase.

Ghalambor M.A., Heath E.C.

J Biol Chem 241:3216-3221(1966) [PubMed] [EuropePMC]
Catalytic mechanism of CMP:2-keto-3-deoxy-manno-octonic acid synthetase as derived from complexes with reaction educt and product.

Jelakovic S., Schulz G.E.

The activation of the sugar 2-keto-3-deoxy-manno-octonic acid (Kdo) is catalyzed by CMP-Kdo synthetase (EC 2.7.7.38) and results in a monophosphate diester with CMP. The enzyme is a pharmaceutical target because CMP-Kdo is required for the biosynthesis of lipopolysaccharides that are vital for Gra ... >> More

The activation of the sugar 2-keto-3-deoxy-manno-octonic acid (Kdo) is catalyzed by CMP-Kdo synthetase (EC 2.7.7.38) and results in a monophosphate diester with CMP. The enzyme is a pharmaceutical target because CMP-Kdo is required for the biosynthesis of lipopolysaccharides that are vital for Gram-negative bacteria. We have established the structures of an enzyme complex with the educt CTP and of a complex with the product CMP-Kdo by X-ray diffraction analyses at 100 K, both at 2.6 A resolution. The N-terminal domains of the dimeric enzyme bind CTP in a peculiar nucleotide-binding fold with the beta- and gamma-phosphates located at the so-called "PP-loop", whereas the C-terminal domains participate in Kdo binding and in the dimer interface. The unstable nucleotide-sugar CMP-Kdo was produced in a crystal and stabilized by freezing to 100 K. Its formation is accompanied by an induced fit involving mainchain displacements in the 2 A range. The observed binding conformations together with the amino acid conservation pattern during evolution and the putative location of the required Mg(2+) ion suggest a reaction pathway. The enzyme is structurally homologous to the CMP-N-acetylneuraminic acid synthetases in all parts except for the dimer interface. Moreover, the chainfold and the substrate-binding positions resemble those of other enzymes processing nucleotide sugars. << Less

Biochemistry 41:1174-1181(2002) [PubMed] [EuropePMC]
Structure-based mechanism of CMP-2-keto-3-deoxymanno-octulonic acid synthetase: convergent evolution of a sugar-activating enzyme with DNA/RNA polymerases.

Heyes D.J., Levy C., Lafite P., Roberts I.S., Goldrick M., Stachulski A.V., Rossington S.B., Stanford D., Rigby S.E., Scrutton N.S., Leys D.

The enzyme CMP-Kdo synthetase (KdsB) catalyzes the addition of 2-keto-3-deoxymanno-octulonic acid (Kdo) to CTP to form CMP-Kdo, a key reaction in the biosynthesis of lipopolysaccharide. The reaction catalyzed by KdsB and the related CMP-acylneuraminate synthase is unique among the sugar-activating ... >> More

The enzyme CMP-Kdo synthetase (KdsB) catalyzes the addition of 2-keto-3-deoxymanno-octulonic acid (Kdo) to CTP to form CMP-Kdo, a key reaction in the biosynthesis of lipopolysaccharide. The reaction catalyzed by KdsB and the related CMP-acylneuraminate synthase is unique among the sugar-activating enzymes in that the respective sugars are directly coupled to a cytosine monophosphate. Using inhibition studies, in combination with isothermal calorimetry, we show the substrate analogue 2beta-deoxy-Kdo to be a potent competitive inhibitor. The ligand-free Escherichia coli KdsB and ternary complex KdsB-CTP-2beta-deoxy-Kdo crystal structures reveal that Kdo binding leads to active site closure and repositioning of the CTP phosphates and associated Mg(2+) ion (Mg-B). Both ligands occupy conformations compatible with an S(n)2-type attack on the alpha-phosphate by the Kdo 2-hydroxyl group. Based on strong similarity with DNA/RNA polymerases, both in terms of overall chemistry catalyzed as well as active site configuration, we postulate a second Mg(2+) ion (Mg-A) is bound by the catalytically competent KdsB-CTP-Kdo ternary complex. Modeling of this complex reveals the Mg-A coordinated to the conserved Asp(100) and Asp(235) in addition to the CTP alpha-phosphate and both the Kdo carboxylic and 2-hydroxyl groups. EPR measurements on the Mn(2+)-substituted ternary complex support this model. We propose the KdsB/CNS sugar-activating enzymes catalyze the formation of activated sugars, such as the abundant CMP-5-N-acetylneuraminic acid, by recruitment of two Mg(2+) to the active site. Although each metal ion assists in correct positioning of the substrates and activation of the alpha-phosphate, Mg-A is responsible for activation of the sugar-hydroxyl group. << Less

J Biol Chem 284:35514-35523(2009) [PubMed] [EuropePMC]
Cloning and characterization of cytidine monophosphate-3-deoxy-d-manno-octulosonate synthetase from Arabidopsis thaliana.

Misaki R., Kajiura H., Fujii K., Fujiyama K., Seki T.

The function and metabolic pathway of 3-deoxy-d-manno-octulosonate (KDO) are unclear in plants although it is an essential component in plant cell wall. Here we cloned and characterized a putative Arabidopsis thaliana cytidine monophosphate-KDO synthetase to understand synthetic pathways of KDO. I ... >> More

The function and metabolic pathway of 3-deoxy-d-manno-octulosonate (KDO) are unclear in plants although it is an essential component in plant cell wall. Here we cloned and characterized a putative Arabidopsis thaliana cytidine monophosphate-KDO synthetase to understand synthetic pathways of KDO. It showed a ubiquitous expression, the activity at an optimal pH of 8.0, and a requirement of Mg2+. << Less

J. Biosci. Bioeng. 108:527-529(2009) [PubMed] [EuropePMC]
Structure of 3-deoxy-manno-octulosonate cytidylyltransferase from Haemophilus influenzae complexed with the substrate 3-deoxy-manno-octulosonate in the beta-configuration.

Yoon H.J., Ku M.J., Mikami B., Suh S.W.

The enzyme 3-deoxy-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase; CKS) catalyzes the activation of 3-deoxy-D-manno-octulosonate (or 2-keto-3-deoxy-manno-octonic acid; KDO) by forming CMP-KDO. CKS is unique to Gram-negative bacteria and is an attractive target for the development of a ... >> More

The enzyme 3-deoxy-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase; CKS) catalyzes the activation of 3-deoxy-D-manno-octulosonate (or 2-keto-3-deoxy-manno-octonic acid; KDO) by forming CMP-KDO. CKS is unique to Gram-negative bacteria and is an attractive target for the development of antibacterial agents. The crystal structure of CKS from Haemophilus influenzae in complex with the substrate KDO has been determined at 2.30 A resolution by combining single-wavelength anomalous diffraction and molecular-replacement methods. The two monomers in the asymmetric unit differ in the conformation of their C-terminal alpha-helix (Ala230-Asn254). The KDO bound to the active site exists as the beta-pyranose form in the (5)C(2) chair conformation. The structure of CKS from H. influenzae in complex with KDO will be useful in structure-based inhibitor design. << Less

Acta Crystallogr D Biol Crystallogr 64:1292-1294(2008) [PubMed] [EuropePMC]

RHEA:23448 3-deoxy-alpha-D-manno-oct-2-ulosonate + CTP = CMP-3-deoxy-beta-D-manno-octulosonate + diphosphate

Enzymes

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Cross-references

Publications

The biosynthesis of cell wall lipopolysaccharide in Escherichia coli. IV. Purification and properties of cytidine monophosphate 3-deoxy-d-manno-octulosonate synthetase.

Catalytic mechanism of CMP:2-keto-3-deoxy-manno-octonic acid synthetase as derived from complexes with reaction educt and product.

Structure-based mechanism of CMP-2-keto-3-deoxymanno-octulonic acid synthetase: convergent evolution of a sugar-activating enzyme with DNA/RNA polymerases.

Cloning and characterization of cytidine monophosphate-3-deoxy-d-manno-octulosonate synthetase from Arabidopsis thaliana.

Structure of 3-deoxy-manno-octulosonate cytidylyltransferase from Haemophilus influenzae complexed with the substrate 3-deoxy-manno-octulosonate in the beta-configuration.