Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase By Reference

UDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase catalyzes the first step in the biosynthesis of lipid A, the hydrophobic anchor of lipopolysaccharide in Gram-negative bacteria. This enzyme, the product of the lpxA gene, transfers an R-3-hydroxyacyl chain fromR-3-hydroxyacyl-acyl carrier protein (ACP) to the glucosamine 3-OH of UDP-GlcNAc. The acylation of UDP-GlcNAc is characterized by an unfavorable equilibrium constant (0.01). Therefore, the second reaction of lipid A biosynthesis, in which the LpxA product UDP-3-O-(R-3-hydroxyacyl)-GlcNAc is deacetylated, is the first irreversible step of the pathway. Lipid A is required for growth of E. coli and most other Gram-negative bacteria. Lipid A is also necessary for maintaining the integrity of the outer membrane as a barrier to toxic chemicals. Furthermore, lipid A is a potent activator of innate immunity in animal systems. The study of the enzymes involved in lipid A biosynthesis should therefore prove useful for the development of new anti-infective drugs.




• Summary
• Step 1
• Step 2
• Products

His125 deprotonates UDP-N-acetyl-D-glucosamine hydroxyl group, initiating a nucleophilic attack on the carbonyl carbon of the ACP in an addition reaction. The oxyanion collapses, eliminating ACP with concomitant deprotonation of His125.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Gly	P0A722	143	1lxa	143
Asp	P0A722	126	1lxa	126
His	P0A722	125	1lxa	125

Step Components

overall reactant used, proton transfer, unimolecular elimination by the conjugate base, overall product formed, bimolecular nucleophilic addition, intermediate formation, intermediate terminated, native state of enzyme regenerated



Step 1.

His125 deprotonates UDP-N-acetyl-D-glucosamine hydroxyl group, initiating a nucleophilic attack on the carbonyl carbon of the ACP in an addition reaction.



Step 2.

The oxyanion collapses, eliminating ACP with concomitant deprotonation of His125.



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

• Metabolomic and transcriptomic analyses of Fmo5-/- mice reveal roles for flavin-containing monooxygenase 5 (FMO5) in NRF2-mediated oxidative stress response, unfolded protein response, lipid homeostasis, and carbohydrate and one-carbon metabolism.
• Promiscuous Enzymes for Residue-Specific Peptide and Protein Late-Stage Functionalization.
• Lipid A structural diversity among members of the genus Leptospira.
• Emerging field: O-GlcNAcylation in ferroptosis.
• Genome taxonomy of the genus Thalassotalea and proposal of Thalassotalea hakodatensis sp. nov. isolated from sea cucumber larvae.
• Regulation of Ferroptosis in Lung Adenocarcinoma.
• Mechanisms of low susceptibility to the disinfectant benzalkonium chloride in a multidrug-resistant environmental isolate of Aeromonas hydrophila.
• Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa.
• Availability of iron ions impacts physicochemical properties and proteome of outer membrane vesicles released by Neisseria gonorrhoeae.
• Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions.
• Newest perspectives of glycopeptide antibiotics: biosynthetic cascades, novel derivatives, and new appealing antimicrobial applications.