Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Active Motif

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 10 November 1995:
Vol. 270. no. 5238, pp. 997 - 1000
DOI: 10.1126/science.270.5238.997
Prev | Table of Contents | Next

Reports

A Left-Handed Parallel Helix in the Structure of UDP-N-Acetylglucosamine Acyltransferase

Christian R. H. Raetz and Steven L. Roderick (1)

UDP-N-acetylglucosamine 3-O-acyltransferase (LpxA) catalyzes the transfer of (R)-3-hydroxymyristic acid from its acyl carrier protein thioester to UDP-N-acetylglucosamine. LpxA is the first enzyme in the lipid A biosynthetic pathway and is a target for the design of antibiotics. The x-ray crystal structure of LpxA has been determined to 2.6 angstrom resolution and reveals a domain motif composed of parallel beta strands, termed a left-handed parallel beta helix (LbetaH). This unusual fold displays repeated violations of the protein folding constraint requiring right-handed crossover connections between strands of parallel beta sheets and may be present in other enzymes that share amino acid sequence homology to the repeated hexapeptide motif of LpxA.


C. R. H. Raetz, Department of Biochemistry, Duke University Medical Center, Durham, NC 22710, USA.
S. L. Roderick, Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
(1) To whom correspondence should be addressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Aeromonas hydrophila wb*O34 Gene Cluster: Genetics and Temperature Regulation.
N. Jimenez, R. Canals, M. T. Salo, S. Vilches, S. Merino, and J. M. Tomas (2008)
J. Bacteriol. 190, 4198-4209
   Abstract »    Full Text »    PDF »
Genetic and Clinical Heterogeneity in eIF2B-Related Disorder.
J. Maletkovic, R. Schiffmann, J. R. Gorospe, E. S. Gordon, M. Mintz, E. P. Hoffman, G. Alper, D. R. Lynch, B. S. Singhal, C. Harding, et al. (2008)
J Child Neurol 23, 205-215
   Abstract »    PDF »
Profile of Christian R. H. Raetz.
N. Zagorski (2007)
PNAS 104, 17252-17254
   Full Text »    PDF »
Selection of transposon mutants of Mycobacterium tuberculosis with increased macrophage infectivity identifies fadD23 to be involved in sulfolipid production and association with macrophages.
J. Lynett and R. W. Stokes (2007)
Microbiology 153, 3133-3140
   Abstract »    Full Text »    PDF »
Inaugural Article: Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase.
A. H. Williams and C. R. H. Raetz (2007)
PNAS 104, 13543-13550
   Abstract »    Full Text »    PDF »
Biochemical Characterization of Thepolysialic Acid-specific O-Acetyltransferase NeuO of Escherichia coli K1.
A. K. Bergfeld, H. Claus, U. Vogel, and M. Muhlenhoff (2007)
J. Biol. Chem. 282, 22217-22227
   Abstract »    Full Text »    PDF »
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids.
I. W. Davis, A. Leaver-Fay, V. B. Chen, J. N. Block, G. J. Kapral, X. Wang, L. W. Murray, W. B. Arendall III, J. Snoeyink, J. S. Richardson, et al. (2007)
Nucleic Acids Res. 35, W375-W383
   Abstract »    Full Text »    PDF »
Structure of the E. coli bifunctional GlmU acetyltransferase active site with substrates and products.
L. R. Olsen, M. W. Vetting, and S. L. Roderick (2007)
Protein Sci. 16, 1230-1235
   Abstract »    Full Text »    PDF »
Structure and reactivity of LpxD, the N-acyltransferase of lipid A biosynthesis.
L. Buetow, T. K. Smith, A. Dawson, S. Fyffe, and W. N. Hunter (2007)
PNAS 104, 4321-4326
   Abstract »    Full Text »    PDF »
Side Chain-dependent Stacking Modulates Tau Filament Structure.
M. Margittai and R. Langen (2006)
J. Biol. Chem. 281, 37820-37827
   Abstract »    Full Text »    PDF »
Invited review: Diversity of endotoxin and its impact on pathogenesis.
M. S. Trent, C. M. Stead, A. X. Tran, and J. V. Hankins (2006)
Innate Immunity 12, 205-223
   Abstract »    PDF »
Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide.
A. H. Williams, R. M. Immormino, D. T. Gewirth, and C. R. H. Raetz (2006)
PNAS 103, 10877-10882
   Abstract »    Full Text »    PDF »
Molecular Dynamics Simulations Indicate a Possible Role of Parallel {beta}-Helices in Seeded Aggregation of Poly-Gln.
M. Stork, A. Giese, H. A. Kretzschmar, and P. Tavan (2005)
Biophys. J. 88, 2442-2451
   Abstract »    Full Text »    PDF »
The Structure and Mechanism of Serine Acetyltransferase from Escherichia coli.
V. E. Pye, A. P. Tingey, R. L. Robson, and P. C. E. Moody (2004)
J. Biol. Chem. 279, 40729-40736
   Abstract »    Full Text »    PDF »
Enzymatic Synthesis of Lipid A Molecules with Four Amide-linked Acyl Chains: LpxA ACYLTRANSFERASES SELECTIVE FOR AN ANALOG OF UDP-N-ACETYLGLUCOSAMINE IN WHICH AN AMINE REPLACES THE 3''-HYDROXYL GROUP.
C. R. Sweet, A. H. Williams, M. J. Karbarz, C. Werts, S. R. Kalb, R. J. Cotter, and C. R. H. Raetz (2004)
J. Biol. Chem. 279, 25411-25419
   Abstract »    Full Text »    PDF »
A Methylated Phosphate Group and Four Amide-linked Acyl Chains in Leptospira interrogans Lipid A: THE MEMBRANE ANCHOR OF AN UNUSUAL LIPOPOLYSACCHARIDE THAT ACTIVATES TLR2.
N. L. S. Que-Gewirth, A. A. Ribeiro, S. R. Kalb, R. J. Cotter, D. M. Bulach, B. Adler, I. S. Girons, C. Werts, and C. R. H. Raetz (2004)
J. Biol. Chem. 279, 25420-25429
   Abstract »    Full Text »    PDF »
Properties of GDP-mannose Pyrophosphorylase, a Critical Enzyme and Drug Target in Leishmania mexicana.
A. J. Davis, M. A. Perugini, B. J. Smith, J. D. Stewart, T. Ilg, A. N. Hodder, and E. Handman (2004)
J. Biol. Chem. 279, 12462-12468
   Abstract »    Full Text »    PDF »
Zinc binding drives the folding and association of the homo-trimeric {gamma}-carbonic anhydrase from Methanosarcina thermophila.
B.R. Simler, B. L. Doyle, and C.R. Matthews (2004)
Protein Eng. Des. Sel. 17, 285-291
   Abstract »    Full Text »    PDF »
Structural Basis of Synercid(R) (Quinupristin-Dalfopristin) Resistance in Gram-positive Bacterial Pathogens.
L. E. Kehoe, J. Snidwongse, P. Courvalin, J. B. Rafferty, and I. A. Murray (2003)
J. Biol. Chem. 278, 29963-29970
   Abstract »    Full Text »    PDF »
Genetic Variation at the O-Antigen Biosynthetic Locus in Pseudomonas aeruginosa.
C. K. Raymond, E. H. Sims, A. Kas, D. H. Spencer, T. V. Kutyavin, R. G. Ivey, Y. Zhou, R. Kaul, J. B. Clendenning, and M. V. Olson (2002)
J. Bacteriol. 184, 3614-3622
   Abstract »    Full Text »    PDF »
Relaxed Acyl Chain Specificity of Bordetella UDP-N-acetylglucosamine Acyltransferases.
C. R. Sweet, A. Preston, E. Toland, S. M. Ramirez, R. J. Cotter, D. J. Maskell, and C. R. H. Raetz (2002)
J. Biol. Chem. 277, 18281-18290
   Abstract »    Full Text »    PDF »
Acyl group specificity at the active site of tetrahydridipicolinate N-succinyltransferase.
T. W. Beaman, K. W. Vogel, D. G. Drueckhammer, J. S. Blanchard, and S. L. Roderick (2002)
Protein Sci. 11, 974-979
   Abstract »    Full Text »    PDF »
Structural studies of the scrapie prion protein by electron crystallography.
H. Wille, M. D. Michelitsch, V. Guenebaut, S. Supattapone, A. Serban, F. E. Cohen, D. A. Agard, and S. B. Prusiner (2002)
PNAS 99, 3563-3568
   Abstract »    Full Text »    PDF »
Site-Specific Amino Acid Replacement Matrices from Structurally Constrained Protein Evolution Simulations.
M. S. Fornasari, G. Parisi, and J. Echave (2002)
Mol. Biol. Evol. 19, 352-356
   Abstract »    Full Text »    PDF »
Polymorphisms in Pilin Glycosylation Locus of Neisseria meningitidis Expressing Class II Pili.
C. M. Kahler, L. E. Martin, Y.-L. Tzeng, Y. K. Miller, K. Sharkey, D. S. Stephens, and J. K. Davies (2001)
Infect. Immun. 69, 3597-3604
   Abstract »    Full Text »    PDF »
Invited review: Lipopolysaccharide biosynthesis: which steps do bacteria need to survive?.
S. Gronow and H. Brade (2001)
Innate Immunity 7, 3-23
   Abstract »    PDF »
The Hans Neurath Award lecture of The Protein Society: Proteins--A testament to physics, chemistry, and evolution.
J. M. Thornton (2001)
Protein Sci. 10, 3-11
   Full Text »
Evidence for Multimerization of Neu Proteins Involved in Polysialic Acid Synthesis in Escherichia coli K1 Using Improved LexA-Based Vectors.
D. A. Daines and R. P. Silver (2000)
J. Bacteriol. 182, 5267-5270
   Abstract »    Full Text »
Identification of Domains and Residues within the varepsilon Subunit of Eukaryotic Translation Initiation Factor 2B (eIF2Bvarepsilon ) Required for Guanine Nucleotide Exchange Reveals a Novel Activation Function Promoted by eIF2B Complex Formation.
E. Gomez and G. D. Pavitt (2000)
Mol. Cell. Biol. 20, 3965-3976
   Abstract »    Full Text »
Serine Acetyltransferase from Escherichia coli Is a Dimer of Trimers.
V. J. Hindson, P. C. E. Moody, A. J. Rowe, and W. V. Shaw (2000)
J. Biol. Chem. 275, 461-466
   Abstract »    Full Text »    PDF »
Characterization of the Gene Encoding Serine Acetyltransferase, a Regulated Enzyme of Cysteine Biosynthesis from the Protist Parasites Entamoeba histolytica and Entamoeba dispar. REGULATION AND POSSIBLE FUNCTION OF THE CYSTEINE BIOSYNTHETIC PATHWAY IN ENTAMOEBA.
T. Nozaki, T. Asai, L. B. Sanchez, S. Kobayashi, M. Nakazawa, and T. Takeuchi (1999)
J. Biol. Chem. 274, 32445-32452
   Abstract »    Full Text »    PDF »
The Active Site of Escherichia coli UDP-N-acetylglucosamine Acyltransferase. CHEMICAL MODIFICATION AND SITE-DIRECTED MUTAGENESIS.
T. J. O. Wyckoff and C. R. H. Raetz (1999)
J. Biol. Chem. 274, 27047-27055
   Abstract »    Full Text »    PDF »
Hydrocarbon Rulers in UDP-N-acetylglucosamine Acyltransferases.
T. J. O. Wyckoff, S. Lin, R. J. Cotter, G. D. Dotson, and C. R. H. Raetz (1998)
J. Biol. Chem. 273, 32369-32372
   Abstract »    Full Text »    PDF »
Probing the Role of Cysteine Residues in Glucosamine-1-Phosphate Acetyltransferase Activity of the Bifunctional GlmU Protein from Escherichia coli: Site-Directed Mutagenesis and Characterization of the Mutant Enzymes.
F. Pompeo, J. van Heijenoort, and D. Mengin-Lecreulx (1998)
J. Bacteriol. 180, 4799-4803
   Abstract »    Full Text »
A New Metabolic Link between Fatty Acid de Novo Synthesis and Polyhydroxyalkanoic Acid Synthesis. THE PHAG GENE FROM PSEUDOMONAS PUTIDA KT2440 ENCODES A 3-HYDROXYACYL-ACYL CARRIER PROTEIN-COENZYME A TRANSFERASE.
B. H. A. Rehm, N. Kruger, and A. Steinbuchel (1998)
J. Biol. Chem. 273, 24044-24051
   Abstract »    Full Text »    PDF »
Acylation of Escherichia coli Hemolysin: A Unique Protein Lipidation Mechanism Underlying Toxin Function.
P. Stanley, V. Koronakis, and C. Hughes (1998)
Microbiol. Mol. Biol. Rev. 62, 309-333
   Abstract »    Full Text »    PDF »
Expression Cloning of a Pseudomonas Gene Encoding a Hydroxydecanoyl-Acyl Carrier Protein-Dependent UDP-GlcNAc Acyltransferase.
G. D. Dotson, I. A. Kaltashov, R. J. Cotter, and C. R. H. Raetz (1998)
J. Bacteriol. 180, 330-337
   Abstract »    Full Text »
Gene Families: The Taxonomy of Protein Paralogs and Chimeras.
S. Henikoff, E. A. Greene, S. Pietrokovski, P. Bork, T. K. Attwood, and L. Hood (1997)
Science 278, 609-614
   Abstract »    Full Text »
Identification of the Gene Encoding the Escherichia coli Lipid A 4'-Kinase. FACILE PHOSPHORYLATION OF ENDOTOXIN ANALOGS WITH RECOMBINANT LpxK.
T. A. Garrett, J. L. Kadrmas, and C. R. H. Raetz (1997)
J. Biol. Chem. 272, 21855-21864
   Abstract »    Full Text »    PDF »
Shortened Hydroxyacyl Chains on Lipid A of Escherichia coli Cells Expressing a Foreign UDP-N-Acetylglucosamine O-Acyltransferase.
T. J. Odegaard, I. A. Kaltashov, R. J. Cotter, L. Steeghs, P. van der Ley, S. Khan, D. J. Maskell, and C. R. H. Raetz (1997)
J. Biol. Chem. 272, 19688-19696
   Abstract »    Full Text »    PDF »
Differential Effect of Site-directed Mutations in pelC on Pectate Lyase Activity, Plant Tissue Maceration, and Elicitor Activity.
N. Kita, C. M. Boyd, M. R. Garrett, F. Jurnak, and N. T. Keen (1996)
J. Biol. Chem. 271, 26529-26535
   Abstract »    Full Text »    PDF »
Function of the htrB High Temperature Requirement Gene of Escherichia coli in the Acylation of Lipid A.
T. Clementz, J. J. Bednarski, and C. R. H. Raetz (1996)
J. Biol. Chem. 271, 12095-12102
   Abstract »    Full Text »    PDF »
Dissection of the Bifunctional Escherichia coli N-Acetylglucosamine-1-phosphate Uridyltransferase Enzyme into Autonomously Functional Domains and Evidence That Trimerization Is Absolutely Required for Glucosamine-1-phosphate Acetyltransferase Activity and Cell Growth.
F. Pompeo, Y. Bourne, J. van Heijenoort, F. Fassy, and D. Mengin-Lecreulx (2001)
J. Biol. Chem. 276, 3833-3839
   Abstract »    Full Text »    PDF »
Identification and Analysis of the Acyl Carrier Protein (ACP) Docking Site on beta -Ketoacyl-ACP Synthase III.
Y.-M. Zhang, M. S. Rao, R. J. Heath, A. C. Price, A. J. Olson, C. O. Rock, and S. W. White (2001)
J. Biol. Chem. 276, 8231-8238
   Abstract »    Full Text »    PDF »
Characterization of Transsulfuration and Cysteine Biosynthetic Pathways in the Protozoan Hemoflagellate, Trypanosoma cruzi. ISOLATION AND MOLECULAR CHARACTERIZATION OF CYSTATHIONINE beta -SYNTHASE AND SERINE ACETYLTRANSFERASE FROM TRYPANOSOMA.
T. Nozaki, Y. Shigeta, Y. Saito-Nakano, M. Imada, and W. D. Kruger (2001)
J. Biol. Chem. 276, 6516-6523
   Abstract »    Full Text »    PDF »
Is Congo Red an Amyloid-specific Dye?.
R. Khurana, V. N. Uversky, L. Nielsen, and A. L. Fink (2001)
J. Biol. Chem. 276, 22715-22721
   Abstract »    Full Text »    PDF »
A Chlamydia trachomatis UDP-N-Acetylglucosamine Acyltransferase Selective for Myristoyl-Acyl Carrier Protein. EXPRESSION IN ESCHERICHIA COLI AND FORMATION OF HYBRID LIPID A SPECIES.
C. R. Sweet, S. Lin, R. J. Cotter, and C. R. H. Raetz (2001)
J. Biol. Chem. 276, 19565-19574
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)