ArticleBiochemistry2010
Activation of Escherichia coli UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase by Fe2+ yields a more efficient enzyme with altered ligand affinity.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 41 citations in OpenAlex.
- Synthesis, Biological Evaluation, and Molecular Docking Studies of 2r,3t,4c-Configured C-Furanosidic LpxC Inhibitors.Archiv der Pharmazie · 2026Article
- The activation of the metal-containing regulatory protein NiaR from Thermotoga maritima by its effector, nicotinic acid.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2025Article
- Recent advances in small molecule LpxC inhibitors against gram-negative bacteria (2014-2024).Frontiers in microbiology · 2025Review
- Development of Fragment-Based Inhibitors of the Bacterial Deacetylase LpxC with Low Nanomolar Activity.Journal of medicinal chemistry · 2024Article
- How Theoretical Evaluations Can Generate Guidelines for Designing/Engineering Metalloproteins with Desired Metal Affinity and Selectivity.Molecules (Basel, Switzerland) · 2022Review
- Structure, inhibition, and regulation of essential lipid A enzymes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- The Metal Drives the Chemistry: Dual Functions of Acireductone Dioxygenase.Chemical reviews · 2017Review
- Kinetics and thermodynamics of metal-binding to histone deacetylase 8.Protein science : a publication of the Protein Society · 2015Article
- The structure- and metal-dependent activity of Escherichia coli PgaB provides insight into the partial de-N-acetylation of poly-β-1,6-N-acetyl-D-glucosamine.The Journal of biological chemistry · 2012Article
- The activity and cofactor preferences of N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) change depending on environmental conditions.The Journal of biological chemistry · 2011Article
- Control of lipopolysaccharide biosynthesis by FtsH-mediated proteolysis of LpxC is conserved in enterobacteria but not in all gram-negative bacteria.Journal of bacteriology · 2011Article
- Active site metal ion in UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) switches between Fe(II) and Zn(II) depending on cellular conditions.The Journal of biological chemistry · 2010Article
- Structures of metal-substituted human histone deacetylase 8 provide mechanistic inferences on biological function .Biochemistry · 2010Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The metal-dependent deacetylase UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) catalyzes the first committed step in lipid A biosynthesis, the hydrolysis of UDP-3-O-myristoyl-N-acetylglucosamine to form UDP-3-O-myristoylglucosamine and acetate. Consequently, LpxC is a target for the development of antibiotics, nearly all of which coordinate the active site metal ion. Here we examine the ability of Fe(2+) to serve as a cofactor for wild-type Escherichia coli LpxC and a mutant enzyme (EcC63A), in which one of the ligands for the inhibitory metal binding site has been removed. LpxC exhibits higher activity (6-8-fold) with a single bound Fe(2+) as the cofactor compared to Zn(2+)-LpxC; both metalloenzymes have a bell-shaped dependence on pH with similar pK(a) values, indicating that at least two ionizations are important for maximal activity. X-ray absorption spectroscopy experiments suggest that the catalytic metal ion bound to Fe(2+)-EcLpxC is five-coordinate, suggesting that catalytic activity may correlate with coordination number. Furthermore, the ligand affinity of Fe(2+)-LpxC compared to the Zn(2+) enzyme is altered by up to 6-fold. In contrast to Zn(2+)-LpxC, the activity of Fe(2+)-LpxC is redox-sensitive, and a time-dependent decrease in activity is observed under aerobic conditions. The LpxC activity of crude E. coli cell lysates is also aerobically sensitive, consistent with the presence of Fe(2+)-LpxC. These data indicate that EcLpxC can use either Fe(2+) or Zn(2+) to activate catalysis in vitro and possibly in vivo, which may allow LpxC to function in E. coli grown under different environmental conditions.
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