lpxC

Summary

Gene Symbol: lpxC
Description: UDP-3-O-acyl N-acetylglucosamine deacetylase
Alias: ECK0097, JW0094, asmB, envA
Species: Escherichia coli str. K-12 substr. MG1655
Products:     lpxC

Top Publications

  1. Li X, Uchiyama T, Raetz C, Hindsgaul O. Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis. Org Lett. 2003;5:539-41 pubmed
    reaction: see text] The enzyme LpxC (UDP-3-O-[(R)-3-hydroxymyristoyl]-GlcNAc deacetylase) catalyzes the second step of lipid A biosynthesis and is essential for bacterial growth...
  2. Young K, Silver L, Bramhill D, Cameron P, Eveland S, Raetz C, et al. The envA permeability/cell division gene of Escherichia coli encodes the second enzyme of lipid A biosynthesis. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase. J Biol Chem. 1995;270:30384-91 pubmed
    The envA gene of Escherichia coli has been shown previously to be essential for cell viability (Beall, B. and Lutkenhaus, J. (1987) J. Bacteriol. 169, 5408-5415), yet it encodes a protein of unknown function...
  3. Coggins B, Li X, McClerren A, Hindsgaul O, Raetz C, Zhou P. Structure of the LpxC deacetylase with a bound substrate-analog inhibitor. Nat Struct Biol. 2003;10:645-51 pubmed
    The zinc-dependent UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) catalyzes the first committed step in the biosynthesis of lipid A, the hydrophobic anchor of lipopolysaccharide (LPS) that constitutes the outermost monolayer of Gram-..
  4. Barb A, McClerren A, Snehelatha K, Reynolds C, Zhou P, Raetz C. Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli. Biochemistry. 2007;46:3793-802 pubmed
    The deacetylation of UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine (UDP-3-O-acyl-GlcNAc) by LpxC is the committed reaction of lipid A biosynthesis...
  5. Hernick M, Gennadios H, Whittington D, Rusche K, Christianson D, Fierke C. UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase functions through a general acid-base catalyst pair mechanism. J Biol Chem. 2005;280:16969-78 pubmed
    UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a zinc-dependent enzyme that catalyzes the deacetylation of UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine to form UDP-3-O-(R-hydroxymyristoyl)glucosamine ..
  6. Lutkenhaus J, Wolf Watz H, Donachie W. Organization of genes in the ftsA-envA region of the Escherichia coli genetic map and identification of a new fts locus (ftsZ). J Bacteriol. 1980;142:615-20 pubmed
    ..amounts of the bacterial deoxyribonucleic acid in this region, it was possible to locate the ftsZ gene between ftsA and envA. It is concluded that these cell division genes are expressed independently of the neighboring murein genes.
  7. Stanley N, Findlay K, Berks B, Palmer T. Escherichia coli strains blocked in Tat-dependent protein export exhibit pleiotropic defects in the cell envelope. J Bacteriol. 2001;183:139-44 pubmed
    ..Both phenotypes are similar to those displayed by strains carrying point mutations in the lpxC (envA) gene...
  8. McClure C, Rusche K, Peariso K, Jackman J, Fierke C, Penner Hahn J. EXAFS studies of the zinc sites of UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC). J Inorg Biochem. 2003;94:78-85 pubmed
    ..has been used to determine the structure of the Zn(II) sites in UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus and Pseudomonas aeruginosa...
  9. Nahlik M, Fleming T, McIntosh M. Cluster of genes controlling synthesis and activation of 2,3-dihydroxybenzoic acid in production of enterobactin in Escherichia coli. J Bacteriol. 1987;169:4163-70 pubmed
    ..A protein of approximately 15,000 daltons appears to be encoded by the chromosomal region adjacent to the entAC gene, but no known function in enterobactin biosynthesis or transport can yet be ascribed to this polypeptide. ..

More Information

Publications53

  1. Ogura T, Inoue K, Tatsuta T, Suzaki T, Karata K, Young K, et al. Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli. Mol Microbiol. 1999;31:833-44 pubmed
    ..by a dramatic increase in the amount of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase [the IpxC (envA) gene product] involved in the committed step of lipid A biosynthesis...
  2. Barb A, Jiang L, Raetz C, Zhou P. Assignment of 1H, 13C and 15N backbone resonances of Escherichia coli LpxC bound to L-161,240. Biomol NMR Assign. 2010;4:37-40 pubmed publisher
    The UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase LpxC catalyzes the committed reaction of lipid A biosynthesis, an essential pathway in Gram-negative bacteria...
  3. Jackman J, Raetz C, Fierke C. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase of Escherichia coli is a zinc metalloenzyme. Biochemistry. 1999;38:1902-11 pubmed
    The enzyme UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase (LpxC) catalyzes the committed step in the biosynthesis of lipid A and is therefore a potential antibiotic target. Inhibition of this enzyme by hydroxamate compounds [Onishi, H...
  4. McClerren A, Endsley S, Bowman J, Andersen N, Guan Z, Rudolph J, et al. A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin. Biochemistry. 2005;44:16574-83 pubmed
    The zinc-dependent enzyme LpxC catalyzes the deacetylation of UDP-3-O-acyl-GlcNAc, the first committed step of lipid A biosynthesis...
  5. Young K, Silver L. Leakage of periplasmic enzymes from envA1 strains of Escherichia coli. J Bacteriol. 1991;173:3609-14 pubmed
    ..In the detailed characterization of the EnvA permeability phenotype presented here, the envA1 mutation was shown to confer leakage of the periplasmic enzymes ..
  6. Kloser A, Laird M, Misra R. asmB, a suppressor locus for assembly-defective OmpF mutants of Escherichia coli, is allelic to envA (lpxC). J Bacteriol. 1996;178:5138-43 pubmed
    ..Further analyses revealed that the asmB mutations map within the envA (lpxC) gene, which encodes an enzyme needed for the synthesis of the lipid A moiety of lipopolysaccharide (LPS)...
  7. Schnaitman C, Klena J. Genetics of lipopolysaccharide biosynthesis in enteric bacteria. Microbiol Rev. 1993;57:655-82 pubmed
  8. Anderson M, Robertson A, Macher I, Raetz C. Biosynthesis of lipid A in Escherichia coli: identification of UDP-3-O-[(R)-3-hydroxymyristoyl]-alpha-D-glucosamine as a precursor of UDP-N2,O3-bis[(R)-3-hydroxymyristoyl]-alpha-D-glucosamine. Biochemistry. 1988;27:1908-17 pubmed
    ..Our observations provide strong evidence that UDP-3-O-[(R)-3-hydroxymyristoyl]glucosamine is a true intermediate in the biosynthesis of UDP-2,3-diacyl-GlcN and lipid A...
  9. Sun D, Cohen S, Mani N, Murphy C, Rothstein D. A pathway-specific cell based screening system to detect bacterial cell wall inhibitors. J Antibiot (Tokyo). 2002;55:279-87 pubmed
    ..well as fosfomycin, cycloserine, and cefoxitin, induce at concentrations at or below the MIC of a host carrying the envA-mutation, which causes a defect in the outer membrane...
  10. Pirrung M, Tumey L, Raetz C, Jackman J, Snehalatha K, McClerren A, et al. Inhibition of the antibacterial target UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC): isoxazoline zinc amidase inhibitors bearing diverse metal binding groups. J Med Chem. 2002;45:4359-70 pubmed
    UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase (LpxC) is a zinc amidase that catalyzes the second step of lipid A biosynthesis in Gram negative bacteria...
  11. Mengin Lecreulx D, Ayala J, Bouhss A, van Heijenoort J, Parquet C, Hara H. Contribution of the Pmra promoter to expression of genes in the Escherichia coli mra cluster of cell envelope biosynthesis and cell division genes. J Bacteriol. 1998;180:4406-12 pubmed
    ..It was concluded that the transcription of the genes located downstream from ftsW in the mra cluster, from murG to ftsZ, is also mainly (but not exclusively) dependent on the Pmra promoter. ..
  12. Hernick M, Fierke C. Catalytic mechanism and molecular recognition of E. coli UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase probed by mutagenesis. Biochemistry. 2006;45:15240-8 pubmed
    UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metal-dependent deacetylase that catalyzes the hydrolysis of UDP-3-O-myristoyl-N-acetyl-glucosamine to form UDP-3-O-myristoyl-glucosamine and acetate...
  13. Trent M. Biosynthesis, transport, and modification of lipid A. Biochem Cell Biol. 2004;82:71-86 pubmed
  14. Liauw S, Steinberg R. Dephosphorylation of catalytic subunit of cAMP-dependent protein kinase at Thr-197 by a cellular protein phosphatase and by purified protein phosphatase-2A. J Biol Chem. 1996;271:258-63 pubmed
  15. Jackman J, Raetz C, Fierke C. Site-directed mutagenesis of the bacterial metalloamidase UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC). Identification of the zinc binding site. Biochemistry. 2001;40:514-23 pubmed
    UDP-3-O-(acyl)-N-acetylglucosamine deacetylase (LpxC) catalyzes the second step in the biosynthesis of lipid A in Gram-negative bacteria...
  16. Kodali S, Galgoci A, Young K, Painter R, Silver L, Herath K, et al. Determination of selectivity and efficacy of fatty acid synthesis inhibitors. J Biol Chem. 2005;280:1669-77 pubmed
    ..2 to 0.4 microg/ml. Furthermore, the effectiveness, selectivity, and the in vitro and in vivo correlations of BABX as well as other fatty acid inhibitors were elucidated, which will aid in future drug discovery...
  17. Jackman J, Fierke C, Tumey L, Pirrung M, Uchiyama T, Tahir S, et al. Antibacterial agents that target lipid A biosynthesis in gram-negative bacteria. Inhibition of diverse UDP-3-O-(r-3-hydroxymyristoyl)-n-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs. J Biol Chem. 2000;275:11002-9 pubmed
    UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) catalyzes the second step in the biosynthesis of lipid A, a unique amphiphilic molecule found in the outer membranes of virtually all Gram-negative bacteria...
  18. Führer F, Langklotz S, Narberhaus F. The C-terminal end of LpxC is required for degradation by the FtsH protease. Mol Microbiol. 2006;59:1025-36 pubmed
    Lipopolysaccharide (LPS) biosynthesis is essential in Gram negative bacteria. LpxC, the key enzyme in LPS formation, catalyses the limiting reaction and controls the ratio between LPS and phospholipids...
  19. Vicente M, Gomez M, Ayala J. Regulation of transcription of cell division genes in the Escherichia coli dcw cluster. Cell Mol Life Sci. 1998;54:317-24 pubmed
    ..extension of the transcripts initiated at the up-stream promoter (mraZ1p) even to the furthest down-stream gene (envA). Complementation tests suggest that they extend into ftsW in the central part of the cluster...
  20. Clements J, Coignard F, Johnson I, Chandler S, Palan S, Waller A, et al. Antibacterial activities and characterization of novel inhibitors of LpxC. Antimicrob Agents Chemother. 2002;46:1793-9 pubmed
    ..UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metalloenzyme that catalyzes the second step in the biosynthesis of lipid A...
  21. Zeng D, Zhao J, Chung H, Guan Z, Raetz C, Zhou P. Mutants resistant to LpxC inhibitors by rebalancing cellular homeostasis. J Biol Chem. 2013;288:5475-86 pubmed publisher
    b>LpxC, the deacetylase that catalyzes the second and committed step of lipid A biosynthesis in Escherichia coli, is an essential enzyme in virtually all gram-negative bacteria and is one of the most promising antibiotic targets for ..
  22. McClerren A, Zhou P, Guan Z, Raetz C, Rudolph J. Kinetic analysis of the zinc-dependent deacetylase in the lipid A biosynthetic pathway. Biochemistry. 2005;44:1106-13 pubmed
    ..first committed step of lipid A biosynthesis in Gram-negative bacteria is catalyzed by the zinc-dependent hydrolase LpxC that removes an acetate from the nitrogen at the 2' '-position of UDP-3-O-acyl-N-acetylglucosamine...
  23. Sorensen P, Lutkenhaus J, Young K, Eveland S, Anderson M, Raetz C. Regulation of UDP-3-O-[R-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase in Escherichia coli. The second enzymatic step of lipid a biosynthesis. J Biol Chem. 1996;271:25898-905 pubmed
    ..The underacylated lipid A-like disaccharide precursors that accumulate during inhibition of Kdo formation may be sufficient to exert normal feedback control. ..
  24. Barb A, Leavy T, Robins L, Guan Z, Six D, Zhou P, et al. Uridine-based inhibitors as new leads for antibiotics targeting Escherichia coli LpxC. Biochemistry. 2009;48:3068-77 pubmed publisher
    The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC catalyzes the committed reaction of lipid A (endotoxin) biosynthesis in Gram-negative bacteria and is a validated antibiotic target...
  25. Hara H, Yasuda S, Horiuchi K, Park J. A promoter for the first nine genes of the Escherichia coli mra cluster of cell division and cell envelope biosynthesis genes, including ftsI and ftsW. J Bacteriol. 1997;179:5802-11 pubmed
    ..Although several potential promoter sequences in this region of the mra cluster have been reported, we conclude that the promoter identified in this study is required for the first nine genes of the cluster to be fully expressed. ..
  26. Pirrung M, Tumey L, McClerren A, Raetz C. High-throughput catch-and-release synthesis of oxazoline hydroxamates. Structure-activity relationships in novel inhibitors of Escherichia coli LpxC: in vitro enzyme inhibition and antibacterial properties. J Am Chem Soc. 2003;125:1575-86 pubmed
    b>LpxC is a zinc amidase that catalyses the second step of lipid A biosynthesis in Gram-negative bacteria...
  27. Yi Q, Lutkenhaus J. The nucleotide sequence of the essential cell-division gene ftsZ of Escherichia coli. Gene. 1985;36:241-7 pubmed
    ..Also located on this DNA fragment is the 3' end of the ftsA gene and the 5' end of the envA gene...
  28. Anderson M, Bulawa C, Raetz C. The biosynthesis of gram-negative endotoxin. Formation of lipid A precursors from UDP-GlcNAc in extracts of Escherichia coli. J Biol Chem. 1985;260:15536-41 pubmed
    ..No reaction is detected with fatty acyl-CoA or free fatty acid. The fatty acylation of sugar nucleotides has not been reported previously in E. coli or any other organism. ..
  29. Beall B, Lutkenhaus J. Sequence analysis, transcriptional organization, and insertional mutagenesis of the envA gene of Escherichia coli. J Bacteriol. 1987;169:5408-15 pubmed
    The Escherichia coli cell permeability-cell separation gene envA and the region immediately downstream were sequenced...
  30. Kadam R, Shivange A, Roy N. Escherichia coli versus Pseudomonas aeruginosa deacetylase LpxC inhibitors selectivity: surface and cavity-depth-based analysis. J Chem Inf Model. 2007;47:1215-24 pubmed
    Although Escherichia coli and Pseudomonas aeruginosa LpxC share sequence and functional similarity, E. coli LpxC inhibitiors are ineffective against P. aeruginosa LpxC...
  31. Barb A, Zhou P. Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis. Curr Pharm Biotechnol. 2008;9:9-15 pubmed
    ..target is the zinc-dependent metalloamidase UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC), which catalyzes the committed step of lipid A (endotoxin) biosynthesis...
  32. Sullivan N, Donachie W. Transcriptional organization within an Escherichia coli cell division gene cluster: direction of transcription of the cell separation gene envA. J Bacteriol. 1984;160:724-32 pubmed
    ..We located the envA cell division gene and its promoter within the cluster and determined the direction of transcription of the gene by ..
  33. Herring C, Blattner F. Conditional lethal amber mutations in essential Escherichia coli genes. J Bacteriol. 2004;186:2673-81 pubmed
    ..We demonstrate the method with the genes frr, gcpE, lpxC, map, murA, ppa, and rpsA. We were unable to isolate an amber mutation in ftsZ...
  34. Normark S. Transduction and dominance studies of the envA gene present in a chain-forming mutant of Escherichia coli K 12. J Gen Microbiol. 1969;57:xxx pubmed
  35. Onishi H, Pelak B, Gerckens L, Silver L, Kahan F, Chen M, et al. Antibacterial agents that inhibit lipid A biosynthesis. Science. 1996;274:980-2 pubmed
    ..coli. ..
  36. Führer F, Muller A, Baumann H, Langklotz S, Kutscher B, Narberhaus F. Sequence and length recognition of the C-terminal turnover element of LpxC, a soluble substrate of the membrane-bound FtsH protease. J Mol Biol. 2007;372:485-96 pubmed
    The membrane-anchored FtsH protease is essential in Escherichia coli as it adjusts the cellular amount of LpxC, the key enzyme in lipopolysaccharide (LPS) biosynthesis. Both accumulation and depletion of LpxC are toxic to E. coli...
  37. Kloser A, Laird M, Deng M, Misra R. Modulations in lipid A and phospholipid biosynthesis pathways influence outer membrane protein assembly in Escherichia coli K-12. Mol Microbiol. 1998;27:1003-8 pubmed
    ..One such assembly suppressor mutation, asmB1, is an allele of lpxC (envA) whose product catalyses the first rate-limiting step in the lipid A (LPS) biosynthesis pathway...
  38. Wang W, Maniar M, Jain R, Jacobs J, Trias J, Yuan Z. A fluorescence-based homogeneous assay for measuring activity of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase. Anal Biochem. 2001;290:338-46 pubmed
    UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is one of the key enzymes of bacterial lipid A biosynthesis, catalyzing the removal of the N-acetyl group of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine...
  39. Lutkenhaus J, Wu H. Determination of transcriptional units and gene products from the ftsA region of Escherichia coli. J Bacteriol. 1980;143:1281-8 pubmed
    Lambda transducing phage gamma 16-2 carries the genes envA, ftsZ, ftsA, ddl, and murC and directs the synthesis of six unique proteins in ultraviolet-irradiated cells...
  40. Raetz C, Reynolds C, Trent M, Bishop R. Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem. 2007;76:295-329 pubmed
    ..Although not required for growth, the modification enzymes modulate virulence of some gram-negative pathogens. Heterologous expression of lipid A modification enzymes may enable the development of new vaccines. ..
  41. Normark S. Genetics of a chain-forming mutant of Escherichia coli. Transduction and dominance of the envA gene mediating increased penetration to some antibacterial agents. Genet Res. 1970;16:63-78 pubmed
  42. Gattis S, Hernick M, Fierke C. 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. J Biol Chem. 2010;285:33788-96 pubmed publisher
    UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) catalyzes the deacetylation of UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine to form UDP-3-O-myristoylglucosamine and acetate in Gram-negative bacteria...
  43. Jung H, Ishino F, Matsuhashi M. Inhibition of growth of ftsQ, ftsA, and ftsZ mutant cells of Escherichia coli by amplification of a chromosomal region encompassing closely aligned cell division and cell growth genes. J Bacteriol. 1989;171:6379-82 pubmed
    ..coli strains with mutations of the flanking cell division genes ftsQ, ftsA, and ftsZ. A shortened fragment in which the major portion of ftsI was deleted also had lethal effects on ftsQ and ftsZ mutants. ..
  44. Hernick M, Fierke C. Molecular recognition by Escherichia coli UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase is modulated by bound metal ions. Biochemistry. 2006;45:14573-81 pubmed
    The metal-dependent enzyme UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) catalyzes the conversion of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine to UDP-3-O-(R-3-hydroxymyristoyl)glucosamine and acetate...