CHRISTIAN RAETZ

Summary

Affiliation: Duke University Medical Center
Country: USA

Publications

  1. ncbi request reprint Regulated covalent modifications of lipid A
    C R Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, NC, USA
    J Endotoxin Res 7:73-8. 2001
  2. pmc Discovery of new biosynthetic pathways: the lipid A story
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, P O Box 3711, Durham, NC 27710, USA
    J Lipid Res 50:S103-8. 2009
  3. pmc Lipopolysaccharide endotoxins
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Biochem 71:635-700. 2002
  4. pmc Lipid A modification systems in gram-negative bacteria
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Biochem 76:295-329. 2007
  5. pmc MsbA transporter-dependent lipid A 1-dephosphorylation on the periplasmic surface of the inner membrane: topography of francisella novicida LpxE expressed in Escherichia coli
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:49470-8. 2004
  6. ncbi request reprint A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function oF UDP-4-deoxy-4-formamido-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:14154-67. 2005
  7. ncbi request reprint A triple mutant of Escherichia coli lacking secondary acyl chains on lipid A
    Mara K Vorachek-Warren
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:14194-205. 2002
  8. pmc An undecaprenyl phosphate-aminoarabinose flippase required for polymyxin resistance in Escherichia coli
    Aixin Yan
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 282:36077-89. 2007
  9. pmc Replacement of lipopolysaccharide with free lipid A molecules in Escherichia coli mutants lacking all core sugars
    C Michael Reynolds
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:9627-40. 2009
  10. pmc A Leptospira interrogans enzyme with similarity to yeast Ste14p that methylates the 1-phosphate group of lipid A
    Middleton Boon Hinckley
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:30214-24. 2005

Research Grants

  1. LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIA
    CHRISTIAN RAETZ; Fiscal Year: 2007
  2. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2007
  3. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2009
  4. LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIA
    CHRISTIAN RAETZ; Fiscal Year: 2009
  5. LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIA
    CHRISTIAN R RAETZ; Fiscal Year: 2010
  6. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2005
  7. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2001
  8. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN R RAETZ; Fiscal Year: 2010

Collaborators

Detail Information

Publications79

  1. ncbi request reprint Regulated covalent modifications of lipid A
    C R Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, NC, USA
    J Endotoxin Res 7:73-8. 2001
    ..We propose that 2-hydroxymyristate released from LPS inside infected animal cells might be converted to 2-hydroxymyristoyl coenzyme A, a potent inhibitor of protein N-myristoyl transferase...
  2. pmc Discovery of new biosynthetic pathways: the lipid A story
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, P O Box 3711, Durham, NC 27710, USA
    J Lipid Res 50:S103-8. 2009
    ....
  3. pmc Lipopolysaccharide endotoxins
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Biochem 71:635-700. 2002
    ..The expanding knowledge of TLR4 specificity and its downstream signaling pathways should provide new opportunities for blocking inflammation associated with infection...
  4. pmc Lipid A modification systems in gram-negative bacteria
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Biochem 76:295-329. 2007
    ..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...
  5. pmc MsbA transporter-dependent lipid A 1-dephosphorylation on the periplasmic surface of the inner membrane: topography of francisella novicida LpxE expressed in Escherichia coli
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:49470-8. 2004
    ..Our findings provide the first direct evidence that lipid A 1-dephosphorylation catalyzed by LpxE occurs on the periplasmic surface of the inner membrane...
  6. ncbi request reprint A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function oF UDP-4-deoxy-4-formamido-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:14154-67. 2005
    ..Because the L-Ara4N unit attached to lipid A is not derivatized with a formyl group, we postulate the existence of a deformylase, acting later in the pathway...
  7. ncbi request reprint A triple mutant of Escherichia coli lacking secondary acyl chains on lipid A
    Mara K Vorachek-Warren
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:14194-205. 2002
    ..MKV15 may prove useful as a host strain for expressing late acyltransferase genes from other Gram-negative bacteria, facilitating the re-engineering of lipid A structure in living cells and the design of novel vaccines...
  8. pmc An undecaprenyl phosphate-aminoarabinose flippase required for polymyxin resistance in Escherichia coli
    Aixin Yan
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 282:36077-89. 2007
    ..PmrM and PmrL, now renamed ArnE and ArnF because of their involvement in L-Ara4N modification of lipid A, may be subunits of an undecaprenyl phosphate-alpha-L-Ara4N flippase...
  9. pmc Replacement of lipopolysaccharide with free lipid A molecules in Escherichia coli mutants lacking all core sugars
    C Michael Reynolds
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:9627-40. 2009
    ..Our findings show that the main function of Kdo is to provide the right substrates for the acyltransferases LpxL and LpxM, resulting in the synthesis of penta- and hexaacylated lipid A, which is optimal for the MsbA flippase...
  10. pmc A Leptospira interrogans enzyme with similarity to yeast Ste14p that methylates the 1-phosphate group of lipid A
    Middleton Boon Hinckley
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:30214-24. 2005
    ..In human cells, engineered to express the individual TLR subtypes, 1-phosphomethyl-lipid A purified from lmtA-expressing E. coli potently activated TLR4 but not TLR2...
  11. ncbi request reprint Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:2886-96. 2002
    ..ArnA resembles UDP-galactose epimerase, dTDP-glucose-4,6-dehydratase, and UDP-xylose synthase in oxidizing the C-4" position of its substrate, but differs in that it releases the NADH product...
  12. ncbi request reprint ATPase activity of the MsbA lipid flippase of Escherichia coli
    William T Doerrler
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:36697-705. 2002
    ..These results provide the first in vitro evidence that MsbA is a lipid-activated ATPase and that hexaacylated lipid A is an especially potent activator...
  13. pmc A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin
    Amanda L McClerren
    Department of Biochemistry, Duke University Medical Center, Post Office Box 3711, Durham, North Carolina 27710, USA
    Biochemistry 44:16574-83. 2005
    ..CHIR-090 is the first example of a slow, tight-binding inhibitor for LpxC and may be the prototype for a new generation of LpxC inhibitors with therapeutic applicability...
  14. ncbi request reprint Kinetic analysis of the zinc-dependent deacetylase in the lipid A biosynthetic pathway
    Amanda L McClerren
    Department of Biochemistry, Duke University Medical Center, P O Box 3813, Durham, North Carolina 27710, USA
    Biochemistry 44:1106-13. 2005
    ..007%, and 0.57%, respectively) suggest that they contribute significantly to catalysis. Our cumulative data support a mechanism for LpxC wherein Glu73 serves as the general base for deprotonation and activation of the zinc-bound water...
  15. pmc Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli
    Adam W Barb
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 46:3793-802. 2007
    ..coli. Given its relatively broad spectrum and potency against diverse Gram-negative pathogens, CHIR-090 is an excellent lead for the further development of new antibiotics targeting the lipid A pathway...
  16. pmc Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis
    Craig M Bartling
    Department of Biochemistry, Duke University Medical Center, P O Box 3711, Durham, North Carolina 27710, USA
    Biochemistry 47:5290-302. 2008
    ..Mutagenesis implicates E. coli H239 but excludes H276 as the catalytic base, and neither residue is likely to stabilize the oxyanion intermediate...
  17. ncbi request reprint Structure of the LpxC deacetylase with a bound substrate-analog inhibitor
    Brian E Coggins
    Department of Biochemistry, Duke University Medical Center, Box 3711 DUMC, 242 Nanaline Duke Building, Research Drive, Durham, North Carolina 27710, USA
    Nat Struct Biol 10:645-51. 2003
    ....
  18. ncbi request reprint MsbA-dependent translocation of lipids across the inner membrane of Escherichia coli
    William T Doerrler
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:45102-9. 2004
    ..Our data showed that MsbA facilitates the rapid translocation of some lipids from the cytoplasmic to the periplasmic side of the inner membrane in living cells...
  19. pmc Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant
    Bing Ma
    Department of Biochemistry, Duke University Medical Center, Box 3711 DUMC, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 105:13823-8. 2008
    ..Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42 degrees C, consistent with a role for LptA in shuttling LPS across the periplasm...
  20. ncbi request reprint A phosphoethanolamine transferase specific for the outer 3-deoxy-D-manno-octulosonic acid residue of Escherichia coli lipopolysaccharide. Identification of the eptB gene and Ca2+ hypersensitivity of an eptB deletion mutant
    C Michael Reynolds
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:21202-11. 2005
    ..Based on its sequence similarity to EptA(PmrC), we propose that the active site of EptB faces the periplasmic surface of the inner membrane...
  21. pmc Uridine-based inhibitors as new leads for antibiotics targeting Escherichia coli LpxC
    Adam W Barb
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:3068-77. 2009
    ..1-68A and a 2-dehydroxy analogue, 1-68Aa, inhibit several purified LpxC orthologues. These compounds may provide new scaffolds for extension of existing LpxC-inhibiting antibiotics to target the UDP binding pocket...
  22. ncbi request reprint An Escherichia coli mutant lacking the cold shock-induced palmitoleoyltransferase of lipid A biosynthesis: absence of unsaturated acyl chains and antibiotic hypersensitivity at 12 degrees C
    Mara K Vorachek-Warren
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:14186-93. 2002
    ..We suggest that the palmitoleoyltransferase may confer a selective advantage upon E. coli cells growing at lower temperatures by making the outer membrane a more effective barrier to harmful chemicals...
  23. pmc Biosynthesis of undecaprenyl phosphate-galactosamine and undecaprenyl phosphate-glucose in Francisella novicida
    Feng Song
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:1173-82. 2009
    ..coli and Salmonella typhimurium...
  24. pmc Expression cloning and periplasmic orientation of the Francisella novicida lipid A 4'-phosphatase LpxF
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:9321-30. 2006
    ..The availability of the lpxF gene will facilitate re-engineering lipid A structures in diverse bacteria...
  25. pmc Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide
    Allison H Williams
    Department of Biochemistry, Duke University Medical Center, Box 3711 DUMC, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:10877-82. 2006
    ..The compact beta-turn structure of peptide 920 bound to LpxA may open previously uncharacterized approaches to the rational design of LpxA inhibitors with antibiotic activity...
  26. ncbi request reprint The Escherichia coli gene encoding the UDP-2,3-diacylglucosamine pyrophosphatase of lipid A biosynthesis
    Kristen J Babinski
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:25937-46. 2002
    ..Because ybbF encodes the specific UDP-2,3-diacylglucosamine hydrolase involved in lipid A biosynthesis, it is now designated lpxH...
  27. ncbi request reprint Accumulation of the lipid A precursor UDP-2,3-diacylglucosamine in an Escherichia coli mutant lacking the lpxH gene
    Kristen J Babinski
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:25947-56. 2002
    ....
  28. pmc Altered lipid A structures and polymyxin hypersensitivity of Rhizobium etli mutants lacking the LpxE and LpxF phosphatases
    Brian O Ingram
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Biochim Biophys Acta 1801:593-604. 2010
    ..Therefore, the dephosphorylation of lipid A molecules in R. etli is not required for nodulation but may instead play a role in protecting the bacteria from cationic antimicrobial peptides or other immune responses of plants...
  29. pmc Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase
    Allison H Williams
    Department of Biochemistry, Duke University Medical Center, Box 3711 DUMC, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 104:13543-50. 2007
    ..0-A structure of LpxA with bound UDP-GlcNAc. Our structures show how LpxA selects for 14-carbon R-3-hydroxyacyl chains and reveal two modes of UDP binding...
  30. ncbi request reprint Inhibition of the antibacterial target UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC): isoxazoline zinc amidase inhibitors bearing diverse metal binding groups
    Michael C Pirrung
    Department of Chemistry, Levine Science Research Center, Box 90317, Duke University, Durham, NC 27708 0317, USA
    J Med Chem 45:4359-70. 2002
    ..Additionally, a designed affinity label inhibits LpxC in a time-dependent manner...
  31. pmc Purification and mutagenesis of LpxL, the lauroyltransferase of Escherichia coli lipid A biosynthesis
    David A Six
    Department of Biochemistry, Duke University Medical Center, P O Box 3711, Durham, North Carolina 27710, USA
    Biochemistry 47:8623-37. 2008
    ..Our results show that the acyltransferases that generate the secondary acyl chains of lipid A are members of the GPAT family and set the stage for structural studies...
  32. ncbi request reprint 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
    Michael C Pirrung
    Department of Chemistry, Levine Science Research Center, Box 90317, Duke University, Durham, North Carolina 27708 0317, USA
    J Am Chem Soc 125:1575-86. 2003
    ..A broad correlation between enzyme inhibitory and antibacterial activity was observed, and novel compounds were discovered that exhibit antibacterial activity but fall outside earlier-known structural classes...
  33. pmc Identification of a chloroform-soluble membrane miniprotein in Escherichia coli and its homolog in Salmonella typhimurium
    Ziqiang Guan
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Anal Biochem 409:284-9. 2011
    ..The methodologies described here may be amendable for detecting and characterizing small hydrophobic proteins in other organisms that are difficult to annotate or analyze by conventional methods...
  34. ncbi request reprint Extraction and identification by mass spectrometry of undecaprenyl diphosphate-MurNAc-pentapeptide-GlcNAc from Escherichia coli
    Ziqiang Guan
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Anal Biochem 345:336-9. 2005
    ....
  35. pmc Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding
    Adam W Barb
    Department of Biochemistry, Duke University Medical Center, Durham NC 27710
    Proc Natl Acad Sci U S A 104:18433-8. 2007
    ..Consistent with this model, we provide evidence that L-161,240 also occupies the hydrophobic passage...
  36. pmc Crystal structure and acyl chain selectivity of Escherichia coli LpxD, the N-acyltransferase of lipid A biosynthesis
    Craig M Bartling
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:8672-83. 2009
    ....
  37. pmc An inner membrane dioxygenase that generates the 2-hydroxymyristate moiety of Salmonella lipid A
    Henry S Gibbons
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 47:2814-25. 2008
    ..LpxO is an unusual example of an integral membrane protein that is a member of the Fe (2+)/O 2/alpha-ketoglutarate-dependent dioxygenase family...
  38. pmc Interchangeable domains in the Kdo transferases of Escherichia coli and Haemophilus influenzae
    Hak Suk Chung
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 49:4126-37. 2010
    ..The N-terminal half of KdtA, especially the first 30 amino acid residues, specifies whether one or two Kdo units are transferred to lipid IV(A)...
  39. pmc Purification and characterization of the lipid A disaccharide synthase (LpxB) from Escherichia coli, a peripheral membrane protein
    Louis E Metzger
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:11559-71. 2009
    ..Mutagenesis of LpxB identified two conserved residues, D89A and R201A, for which no residual catalytic activity was detected. Our results provide a rational starting point for structural studies...
  40. pmc Escherichia coli mutants that synthesize dephosphorylated lipid A molecules
    Brian O Ingram
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 49:8325-37. 2010
    ..Heptose-deficient mutants of E. coli lacking both the 1- and 4'-phosphate moieties are viable on plates but sensitive to CaCl(2). Our methods for reengineering lipid A structure may be useful for generating novel vaccines and adjuvants...
  41. pmc Structural basis for the sugar nucleotide and acyl-chain selectivity of Leptospira interrogans LpxA
    Lori I Robins
    Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, North Carolina 27710, USA
    Biochemistry 48:6191-201. 2009
    ..Our results support the role of LiLpxA H120 (which corresponds to EcLpxA H125) as the catalytic base and provide the first structural information about the orientation of the phosphopantetheine moiety during LpxA catalysis...
  42. ncbi request reprint Loss of outer membrane proteins without inhibition of lipid export in an Escherichia coli YaeT mutant
    William T Doerrler
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:27679-87. 2005
    ..SecA functions as a multicopy suppressor of the temperature-sensitive phenotype and partially restores OM proteins. Our data are consistent with a critical role for YaeT in OM protein assembly in E. coli...
  43. pmc 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
    Charles R Sweet
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:25411-9. 2004
    ..However, UDP-GlcNAc3N is not synthesized in vivo, because E. coli lacks gnnA and gnnB. When the latter are supplied together with A. ferrooxidans lpxA, E. coli incorporates a significant amount of GlcN3N into its lipid A...
  44. ncbi request reprint Origin of lipid A species modified with 4-amino-4-deoxy-L-arabinose in polymyxin-resistant mutants of Escherichia coli. An aminotransferase (ArnB) that generates UDP-4-deoxyl-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:24731-9. 2003
    ..1). ArnB is a member of a very large family of aminotransferases, but closely related ArnB orthologs are present only in those bacteria capable of synthesizing lipid A species modified with the l-Ara4N moiety...
  45. ncbi request reprint Role of Mg2+ and pH in the modification of Salmonella lipid A after endocytosis by macrophage tumour cells
    Henry S Gibbons
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Mol Microbiol 55:425-40. 2005
    ..typhimurium. Our labelling methods should be applicable to studies of lipid A modifications induced by endocytosis of diverse bacteria...
  46. pmc Attenuated virulence of a Francisella mutant lacking the lipid A 4'-phosphatase
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 104:4136-41. 2007
    ..Francisella lpxF mutants may be useful for immunization against tularemia...
  47. pmc Purification and characterization of the lipid A 1-phosphatase LpxE of Rhizobium leguminosarum
    Mark J Karbarz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:414-25. 2009
    ..The availability of purified LpxE will facilitate the preparation of novel 1-dephosphorylated lipid A molecules that are not readily accessible by chemical methods...
  48. pmc A mannosyl transferase required for lipopolysaccharide inner core assembly in Rhizobium leguminosarum. Purification, substrate specificity, and expression in Salmonella waaC mutants
    Margaret I Kanipes
    Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, NC 27710, USA
    J Biol Chem 278:16356-64. 2003
    ..Our results demonstrate that heterologous lpcC expression can be used to modify the structure of the Salmonella and E. coli LPS cores in living cells...
  49. pmc Expression cloning and biochemical characterization of a Rhizobium leguminosarum lipid A 1-phosphatase
    Mark J Karbarz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:39269-79. 2003
    ..leguminosarum symbiosis with plants. Possible orthologs of LpxE are present in some intracellular human pathogens, including Francisella tularensis, Brucella melitensis, and Legionella pneumophila...
  50. ncbi request reprint Refined solution structure of the LpxC-TU-514 complex and pKa analysis of an active site histidine: insights into the mechanism and inhibitor design
    Brian E Coggins
    Department of Biochemistry, Duke University Medical Center, P O Box 3711, 242 Nanaline Duke Building, Research Drive, Durham, North Carolina 27710, USA
    Biochemistry 44:1114-26. 2005
    ..These results provide a structural basis for the design of more potent LpxC inhibitors than those that are currently available...
  51. pmc Relaxed sugar donor selectivity of a Sinorhizobium meliloti ortholog of the Rhizobium leguminosarum mannosyl transferase LpcC. Role of the lipopolysaccharide core in symbiosis of Rhizobiaceae with plants
    Margaret I Kanipes
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 278:16365-71. 2003
    ..meliloti lpsB mutants. Our findings have important implications for the regulation of core glycosylation in S. meliloti and other bacteria containing LpcC orthologs...
  52. pmc Identification of undecaprenyl phosphate-beta-D-galactosamine in Francisella novicida and its function in lipid A modification
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:1162-72. 2009
    ..The discovery of undecaprenyl phosphate-beta-d-GalN suggests Francisella modifies lipid A with GalN on the periplasmic surface of the inner membrane...
  53. pmc An outer membrane enzyme that generates the 2-amino-2-deoxy-gluconate moiety of Rhizobium leguminosarum lipid A
    Nanette L S Que-Gewirth
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:12109-19. 2003
    ..leguminosarum as judged by sucrose gradient analysis. To our knowledge, an oxidase associated with the outer membranes of Gram-negative bacteria has not been reported previously...
  54. pmc An outer membrane enzyme encoded by Salmonella typhimurium lpxR that removes the 3'-acyloxyacyl moiety of lipid A
    C Michael Reynolds
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:21974-87. 2006
    ..coli O157:H7, Yersinia enterocolitica, Helicobacter pylori, and Vibrio cholerae. The function of LpxR is unknown, but it could play a role in pathogenesis because it might modulate the cytokine response of an infected animal...
  55. pmc Expression cloning of three Rhizobium leguminosarum lipopolysaccharide core galacturonosyltransferases
    Suparna Kanjilal-Kolar
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:12865-78. 2006
    ..No in vitro activity was detected when RgtA was expressed in Escherichia coli unless Rhizobiaceae membranes were also included...
  56. pmc Dodecaprenyl phosphate-galacturonic acid as a donor substrate for lipopolysaccharide core glycosylation in Rhizobium leguminosarum
    Suparna Kanjilal-Kolar
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:12879-87. 2006
    ..This work represents the first definitive characterization of a lipid-linked GalA derivative with the proposed structure dodecaprenyl phosphate-beta-D-GalA...
  57. pmc Assignment of 1H, 13C and 15N backbone resonances of Escherichia coli LpxC bound to L-161,240
    Adam W Barb
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Biomol NMR Assign 4:37-40. 2010
    ..The (1)H chemical shifts of complexed L-161,240 are also determined...
  58. pmc Expression cloning and characterization of the C28 acyltransferase of lipid A biosynthesis in Rhizobium leguminosarum
    Shib Sankar Basu
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:28959-71. 2002
    ....
  59. pmc 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
    Nanette L S Que-Gewirth
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:25420-9. 2004
    ..1)H and (31)P NMR analyses revealed that the 1-phosphate group is methylated. Purified L. interrogans lipid A is inactive against human THP-1 cells but does stimulate tumor necrosis factor production by mouse RAW264.7 cells...
  60. pmc An alternative route for UDP-diacylglucosamine hydrolysis in bacterial lipid A biosynthesis
    Louis E Metzger
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 49:6715-26. 2010
    ....
  61. ncbi request reprint Relaxed acyl chain specificity of Bordetella UDP-N-acetylglucosamine acyltransferases
    Charles R Sweet
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:18281-90. 2002
    ..In contrast, LpxA from B. parapertussis did not display relaxed specificity but was selective for C(10)OH-ACP. This study provides an enzymatic explanation for some of the unusual acyl chain variations found in Bordetella lipid A...
  62. pmc Identification of N-acylphosphatidylserine molecules in eukaryotic cells
    Ziqiang Guan
    Department of Biochemistry, Duke University Medical Center, P O Box 3711, Durham, North Carolina 27710, USA
    Biochemistry 46:14500-13. 2007
    ..We suggest that a phospholipase D might cleave N-acyl-PS to generate N-acylserine, in analogy to the biosynthesis of the endocannabinoid N-arachidonoylethanolamine (anadamide) from N-arachidonoylphosphatidylethanolamine...
  63. ncbi request reprint Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, NC, USA
    J Lipid Res 47:1097-111. 2006
    ..Kdo(2)-Lipid A is comparable to LPS by these criteria. Its activity is reduced by >10(3) in cells from TLR-4-deficient mice. The purity of Kdo(2)-Lipid A should facilitate structural analysis of complexes with receptors like TLR-4/MD2...
  64. ncbi request reprint Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A
    An X Tran
    Department of Microbiology, J H Quillen College of Medicine, Johnson City, Tennessee 37614, USA
    J Biol Chem 280:28186-94. 2005
    ..In summary, we demonstrate that attachment of l-Ara4N to the phosphate groups of lipid A and the subsequent resistance to polymyxin is dependent upon the presence of the secondary linked myristoyl group...
  65. ncbi request reprint Potent, novel in vitro inhibitors of the Pseudomonas aeruginosa deacetylase LpxC
    Toni Kline
    Chiron Corporation, 201 Elliot Avenue West, Seattle, WA 98119, USA
    J Med Chem 45:3112-29. 2002
    ..We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors...
  66. pmc Molecular validation of LpxC as an antibacterial drug target in Pseudomonas aeruginosa
    Khisimuzi E Mdluli
    Department of Research Biology, Chiron Corporation, Seattle, WA 98119, USA
    Antimicrob Agents Chemother 50:2178-84. 2006
    ..These data validate P. aeruginosa LpxC as a target for novel antibiotic drugs and should help direct the design of inhibitors against clinically important gram-negative bacteria...
  67. ncbi request reprint Rapid analysis of large protein-protein complexes using NMR-derived orientational constraints: the 95 kDa complex of LpxA with acyl carrier protein
    Nitin U Jain
    Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
    J Mol Biol 343:1379-89. 2004
    ..The structural model generated for this complex can be useful in the design of new anti-bacterial agents that inhibit the biosynthesis of lipid A...
  68. ncbi request reprint Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis
    Xuechen Li
    Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada
    Org Lett 5:539-41. 2003
    ..Compound 8 exhibits activity toward LpxC enzymes from a wider spectrum of bacterial species than any of the previously reported hydroxamic acid inhibitors...
  69. pmc Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesis
    Gareth J Williams
    Centre for Biomolecular Science, The University of St Andrews, UK
    J Biol Chem 280:23000-8. 2005
    ..Our data suggest that the decarboxylase domain catalyzes both hydride abstraction (oxidation) from the C-4' position and the subsequent decarboxylation...
  70. ncbi request reprint Assignment of the 1H, 13C and 15N resonances of the LpxC deacetylase from Aquifex aeolicus in complex with the substrate-analog inhibitor TU-514
    Brian E Coggins
    J Biomol NMR 28:201-2. 2004
  71. ncbi request reprint The lipid lysyl-phosphatidylglycerol is present in membranes of Rhizobium tropici CIAT899 and confers increased resistance to polymyxin B under acidic growth conditions
    Christian Sohlenkamp
    Centro de Ciencias Genomicas, Universidad Nacional Autonoma de Mexico, Av Universidad s n, Apdo Postal 565 A, Cuernavaca, Morelos, CP62210, Mexico
    Mol Plant Microbe Interact 20:1421-30. 2007
    ..When grown in the low-pH medium, lpiA-deficient rhizobial mutants are over four times more susceptible to the cationic peptide polymyxin B than the wild type...
  72. doi request reprint Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily
    Gabriel Schaaf
    Department of Cell and Developmental Biology, School of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7090, USA
    Mol Cell 29:191-206. 2008
    ..Collectively, these findings outline functional mechanisms for the Sec14 superfamily and reveal additional layers of complexity for regulating phosphoinositide homeostasis in eukaryotes...
  73. pmc Periplasmic cleavage and modification of the 1-phosphate group of Helicobacter pylori lipid A
    An X Tran
    Department of Microbiology, J H Quillen College of Medicine, Johnson City, TN 37614, USA
    J Biol Chem 279:55780-91. 2004
    ..pylori lipid A. In summary, we demonstrate that modification of the 1-phosphate group of H. pylori lipid A requires two enzymatic steps...
  74. pmc Solution structure and dynamics of the outer membrane enzyme PagP by NMR
    Peter M Hwang
    Departments of Biochemistry, Medical Genetics and Microbiology, Laboratory Medicine and Pathobiology, and Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Proc Natl Acad Sci U S A 99:13560-5. 2002
    ..This finding is consistent with an emerging paradigm for outer membrane enzymes in providing an adaptive response toward disturbances in the outer membrane...
  75. pmc Origin of the 2-amino-2-deoxy-gluconate unit in Rhizobium leguminosarum lipid A. Expression cloning of the outer membrane oxidase LpxQ
    Nanette L S Que-Gewirth
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:12120-9. 2003
    ..An ortholog of LpxQ is present in the genome of Agrobacterium tumefaciens, as shown by heterologous expression of oxidase activity in E. coli...
  76. pmc Structure and biosynthesis of free lipid A molecules that replace lipopolysaccharide in Francisella tularensis subsp. novicida
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 45:14427-40. 2006
    ..Formation of free lipid A in F. tularensis subsp. novicida might be initiated by an unusual Kdo hydrolase present in the membranes of this organism...
  77. ncbi request reprint Differential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells
    Marie Anne Nahori
    Laboratoire des Spirochètes, Institut Pasteur, Paris, France
    J Immunol 175:6022-31. 2005
    ....
  78. ncbi request reprint Remembering Konrad Bloch
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, 27710, USA
    Biochem Biophys Res Commun 292:1167-70. 2002
  79. ncbi request reprint Oxidation and transamination of the 3"-position of UDP-N-acetylglucosamine by enzymes from Acidithiobacillus ferrooxidans. Role in the formation of lipid a molecules with four amide-linked acyl chains
    Charles R Sweet
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 279:25400-10. 2004
    ..As shown in the accompanying papers, UDP-GlcNAc3N is selectively acylated by LpxAs of A. ferrooxidans, L. interrogans, and M. loti. UDP-GlcNAc3N may be useful as a substrate analog for diverse enzymes that utilize UDP-GlcNAc...

Research Grants20

  1. LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIA
    CHRISTIAN RAETZ; Fiscal Year: 2007
    ..leguminosarum lipid A; and IV) i characterization of enzymes that incorporate the unique inner core sugars of/?, leguminosarum LPS. ..
  2. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2007
    ..These studies should accelerate the development of antibiotics that target the lipid A system and provide fundamental insights into the mechanisms of bacterial membrane assembly. ..
  3. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2009
    ..These studies should accelerate the development of antibiotics that target the lipid A system and provide fundamental insights into the mechanisms of bacterial membrane assembly. ..
  4. LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIA
    CHRISTIAN RAETZ; Fiscal Year: 2009
    ....
  5. LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIA
    CHRISTIAN R RAETZ; Fiscal Year: 2010
    ....
  6. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2005
    ..coli. ..
  7. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN RAETZ; Fiscal Year: 2001
    ....
  8. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    CHRISTIAN R RAETZ; Fiscal Year: 2010
    ....