Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

3-deoxy-8-phosphooctulonate synthase By Reference

3-deoxy-d-manno-s-octulosonate-8-phosphate synthase from Escherichia coli (KDO8P) is responsible for the synthesis of the named product from Phosphenol Pyruvate (PEP) and arabinose-5-phosphate (A5P). It thus plays a role in the synthesis of complex lipids for the gram negative bacterial cell wall, so is a possible target for antibiotics. It displays homology with many PEP utilising enzymes, particularly the metal dependent enzyme DAHP synthase which works by a similar mechanism where a single amino acid change of non-metallo KDO8P changes it to metallo-KDO8P.




• Summary
• Step 1
• Step 2
• Step 3
• Products

The reaction proceeds through an aldol-like condensation where water activated phosphoenolpyruvate attacks A5P. This forms a bis-phosphorylated tetrahedral intermediate recorded in mass spectrometry experiments. The resulting intermediate then collapses, eliminating a phosphate group. Subsequent sugar cyclisation occurs to form KDO8P. By analogy with the Aquifex aeolicus metallo-KDO8P synthase, water by having hydrogen bonds with the phosphate on PEP increases it's nucleophilicity to attack PEP which in turn is positioned for nucleophilic attack by Lys60. Asp250 and Asn26 hydrogen bond and position A5P for the reaction. Asn26 is thought to mimic the metal ion in metallo-KDO8P enzymes.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Asn	P0A715	26	1q3n	26
Lys	P0A715	60	1q3n	60
Asp	P0A715	250	1q3n	250

Step Components

overall reactant used, proton transfer, overall product formed, unimolecular elimination by the conjugate base, intermediate formation, bimolecular nucleophilic substitution, intermediate terminated, intramolecular nucleophilic addition, intermediate collapse



Step 1.

Water acts as a nucleophile and attacks C2 on PEP, activating C3 PEP to attack the reducing end of A5P. The step passes through an oxocarbenium ion-like transition state.



Step 2.

Phosphohemiketal intermediate forms. The tetrahedral intermediate collapses to open chain KDO8P.



Step 3.

Sugar condensation to form the ring structure, 3-Deoxy-D-manno-octulosonate phosphate.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• Understanding the mechanisms of halotolerance in members of Pontixanthobacter and Allopontixanthobacter by comparative genome analysis.
• The Effects of Helicobacter pylori-Derived Outer Membrane Vesicles on Hepatic Stellate Cell Activation and Liver Fibrosis In Vitro.
• Mechanism of Resistance Development in E. coli against TCAT, a Trimethoprim-Based Photoswitchable Antibiotic.
• The gut microbiota composition in patients with right- and left-sided colorectal cancer and after curative colectomy, as analyzed by 16S rRNA gene amplicon sequencing.
• Polyinfection in Fish Aeromoniasis: A Study of Co-Isolated Aeromonas Species in Aeromonas veronii Outbreaks.
• The Astounding World of Glycans from Giant Viruses.
• Effects of Co-culture on Improved Productivity and Bioresource for Microalgal Biomass Using the Floc-Forming Bacteria Melaminivora Jejuensis.
• Identification of QTLs for Domestication-Related Traits in Zombi Pea [Vigna vexillata (L.) A. Rich], a Lost Crop of Africa.
• Comparative Genomics Analyses Support the Reclassification of Bisgaard Taxon 40 as Mergibacter gen. nov., With Mergibacter septicus sp. nov. as Type Species: Novel Insights Into the Phylogeny and Virulence Factors of a Pasteurellaceae Family Member Associated With Mortality Events in Seabirds.
• HbtR, a Heterofunctional Homolog of the Virulence Regulator TcpP, Facilitates the Transition between Symbiotic and Planktonic Lifestyles in Vibrio fischeri.
• Structure of 2-keto-3-deoxy-D-manno-octulosonate-8-phosphate synthase from Pseudomonas aeruginosa.