Structure and reactivity of LpxD, the N -acyltransferase of lipid A biosynthesis

Buetow, Lori; Smith, Terry K.; Dawson, Alice; Fyffe, Stewart; Hunter, William N.

doi:10.1073/pnas.0606356104

Cited by 80Enzyme Structure and FunctionBacterial Genetics and BiotechnologyCarbohydrate Chemistry and Synthesis

Structure and reactivity of LpxD, the N -acyltransferase of lipid A biosynthesis

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Buetow, Lori, Smith, Terry K., Dawson, Alice, Fyffe, Stewart, Hunter, William N.·2007·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0606356104PMC PMC1810333

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Abstract

The external layer of the Gram-negative bacterial outer membrane is primarily composed of a protective, selectively permeable LPS. The biosynthesis of LPS relies on UDP-3- O -acyl-glucosamine N -acyltransferase (LpxD), which transfers 3-hydroxy-arachidic acid from acyl carrier protein to the 2′ amine of UDP-3- O -myristoyl glucosamine in Chlamydia trachomatis . Our crystallographic study reveals that LpxD is a homotrimer, each subunit of which is constructed from a novel combination of an N-terminal uridine-binding domain, a core lipid-binding domain, and a C-terminal helical extension. Highly conserved residues dominate nucleotide binding. Phe-43 and Tyr-49 form π-stacking interactions with uracil, and Asn-46 and His-284 form hydrogen bonds with the phosphate groups. These interactions place the glucosamine moiety at the catalytic center formed by two adjacent subunits. Here His-247 and His-284 contribute to a mechanism involving nucleophilic attack by the amine of one substrate on the carbonyl carbon of an acyl carrier protein thioester conjugate. Serendipitously, our study reveals a fatty acid (FA) binding groove near the catalytic center. MS elucidated the presence of a FA mixture binding to LpxD, with palmitic acid the most prevalent. The placement of UDP- N -acetylglucosamine and the FA provides details of N -acyltransferase ligand interactions and allows for a description of structure and reactivity at an early stage of LPS assembly.

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Expression of genes involved in lipopolysaccharide biosynthesis, especially LpxA and LpxD, was significantly decreased in mice gavaged with live Bacteroides.
“the expression of genes involved in LPS biosynthesis, especially LpxA and LpxD, which are involved in lipid A biosynthesis and constitute the essential acyltransferases of the lipid A structure (Figure 3B), 38,39 was significantly decreased in mice gavaged with live Bacteroides (Figure 3A and 3C, Figure IV in the online-only Data Supplement).”
From Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis (2018) · cites this paper as [39]

[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
PROCHECK: a program to check the stereochemical quality of protein structures
Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889892009944 · Cited by 24,581 · see citing works
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,299 · see citing works
Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features
Kabsch, W., & Sander, C. (1983) · Biopolymers · doi:10.1002/bip.360221211 · Cited by 15,320 · see citing works
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · see citing works
Improved methods for building protein models in electron density maps and the location of errors in these models
Jones, T. A., Zou, J.-Y., Cowan, S. W., & Kjeldgaard, M. (1991) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767390010224 · Cited by 12,650 · see citing works
Heat Shock Protein A12B Protects Vascular Endothelial Cells Against Sepsis-Induced Acute Lung Injury in Mice
Chen, Y., Wang, L., Kang, Q., Zhang, X., Yu, G., Wan, X., Wang, J., & Zhu, K. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477308 · Cited by 10,730 · see citing works
AMoRe: an automated package for molecular replacement
Navaza, J. (1994) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767393007597 · Cited by 4,941 · see citing works
PRODRG: a tool for high-throughput crystallography of protein–ligand complexes
Schüttelkopf, A. W., & van Aalten, D. M. F. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904011679 · Cited by 4,815 · see citing works
Lipopolysaccharide endotoxins
Raetz, C. R. H., & Whitfield, C. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135414 · Cited by 4,404 · see citing works
Automated MAD and MIR structure solution
Terwilliger, T. C., & Berendzen, J. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444999000839 · Cited by 3,038 · see citing works
The immunopathogenesis of sepsis
Cohen, J. (2002) · Nature · doi:10.1038/nature01326 · Cited by 2,742 · see citing works
Principles of protein-protein interactions
Jones, S., & Thornton, J. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.13 · Cited by 2,684 · see citing works
Maximum-likelihood density modification
Terwilliger, T. C. (2000) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444900005072 · Cited by 1,637 · see citing works
Dali: a network tool for protein structure comparison
Holm, L., & Sander, C. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89105-7 · Cited by 1,462 · see citing works
PROMOTIF—A program to identify and analyze structural motifs in proteins
Hutchinson, E. G., & Thornton, J. M. (1996) · Protein Science · doi:10.1002/pro.5560050204 · Cited by 1,054 · see citing works
Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities
Galanos, C., Luderitz, O., Rietschel, E., Westphal, O., Brade, H., Brade, L., Freudenberg, M. A., Schade, U. F., Imoto, M., Yoshimura, H., et al. (1985) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1985.tb08798.x · Cited by 493 · see citing works
Remarks about protein structure precision
Cruickshank, D. W. J. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998012645 · Cited by 484 · see citing works
Antibacterial Agents That Inhibit Lipid A Biosynthesis
Onishi, H. R., PELAK, B. A., Gerckens, L. S., Silver, L. L., Kahan, F. M., Chen, M., Patchett, A. A., Galloway, S. M., Hyland, S. A., Anderson, M. S., et al. (1996) · Science · doi:10.1126/science.274.5289.980 · Cited by 413 · see citing works
A Left-Handed Parallel β Helix in the Structure of UDP- N- Acetylglucosamine Acyltransferase
Raetz, C. R. H., & Roderick, S. L. (1995) · Science · doi:10.1126/science.270.5238.997 · Cited by 320 · see citing works
Crystal structures of substrate binding to Bacillus subtilis holo-(acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites
Parris, K. D., Lin, L., Tam, A., Mathew, R. S., Hixon, J., Stahl, M., Fritz, C., Seehra, J. S., & Somers, W. S. (2000) · Structure · doi:10.1016/s0969-2126(00)00178-7 · Cited by 217 · see citing works
Biosynthesis of lipid A precursors in Escherichia coli. A cytoplasmic acyltransferase that converts UDP-N-acetylglucosamine to UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine.
Anderson, M. S., & Raetz, C. R. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61169-x · Cited by 182 · see citing works
Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis
Whittington, D. A., Rusche, K. M., Shin, H., Fierke, C. A., & Christianson, D. W. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432990100 · Cited by 167 · see citing works
Identification and Analysis of the Acyl Carrier Protein (ACP) Docking Site on β-Ketoacyl-ACP Synthase III
Zhang, Y.-M., Rao, M. S., Heath, R. J., Price, A. C., Olson, A. J., Rock, C. O., & White, S. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008042200 · Cited by 167 · see citing works
Key Residues Responsible for Acyl Carrier Protein and β-Ketoacyl-Acyl Carrier Protein Reductase (FabG) Interaction
Zhang, Y., Wu, B., Zheng, J., & Rock, C. O. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309874200 · Cited by 147 · see citing works
Fatty acid interactions with proteins: what X-ray crystal and NMR solution structures tell us
Hamilton, J. A. (2003) · Progress in Lipid Research · doi:10.1016/j.plipres.2003.09.002 · Cited by 142 · see citing works
The firA gene of Escherichia coli encodes UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase. The third step of endotoxin biosynthesis.
Kelly, T. M., Stachula, S. A., Raetz, C. R. H., & Anderson, M. S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36593-7 · Cited by 137 · see citing works
Structure of the LpxC deacetylase with a bound substrate-analog inhibitor
Coggins, B. E., Li, X., McClerren, A. L., Hindsgaul, O., Raetz, C. R. H., & Zhou, P. (2003) · Nature Structural & Molecular Biology · doi:10.1038/nsb948 · Cited by 122 · see citing works
Structural Analysis of the Lipopolysaccharide fromChlamydia trachomatis Serotype L2
Rund, S., Lindner, B., Brade, H., & Holst, O. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.24.16819 · Cited by 110 · see citing works
Eight bacterial proteins, including UDP-N-acetylglucosamine acyltransferase (LpxA) and three other transferases ofEscherichia coli, consist of a six-residue periodicity theme
Vaara, M. (1992) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1992.tb05471.x · Cited by 105 · see citing works
Molecular mechanisms involved in the pathogenesis of septic shock
López-Bojórquez, L. N., Zentella‐Dehesa, A., & Reyes‐Terán, G. (2004) · Archives of Medical Research · doi:10.1016/j.arcmed.2004.07.006 · Cited by 100 · see citing works
Hydrocarbon Rulers in UDP-N-acetylglucosamine Acyltransferases
Wyckoff, T. J. O., Lin, S., Cotter, R. J., Dotson, G. D., & Raetz, C. R. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.32369 · Cited by 91 · see citing works
Recombinant Human PPAR-β/δ Ligand-binding Domain is Locked in an Activated Conformation by Endogenous Fatty Acids
Fyffe, S. A., Alphey, M. S., Buetow, L., Smith, T. K., Ferguson, M. A. J., Sørensen, M. D., Björkling, F., & Hunter, W. N. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.12.047 · Cited by 83 · see citing works
Self-citation
The Active Site of Escherichia coli UDP-N-acetylglucosamine Acyltransferase
Wyckoff, T. J. O., & Raetz, C. R. H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.38.27047 · Cited by 78 · see citing works
Structure of UDP- N -acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide
Williams, A. H., Immormino, R. M., Gewirth, D. T., & Raetz, C. R. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604465103 · Cited by 67 · see citing works
The novel hexapeptide motif found in the acyltransferases LpxA and LpxD of lipid A biosynthesis is conserved in various bacteria
Vuorio, R., Härkönen, T., Tolvanen, M. E. E., & Vaara, M. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)80211-4 · Cited by 64 · see citing works
Identification and sequence analysis of the gene mutated in the conditionally lethal outer membrane permeability mutant SS‐C of Salmonella typhimurium.
Hirvas, L., Koski, P., & Vaara, M. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb08036.x · Cited by 37 · see citing works
Crystal structure of UDP‐N‐acetylglucosamine acyltransferase fromHelicobacter pylori
Lee, B. I., & Suh, S. W. (2003) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10436 · Cited by 24 · see citing works
Mutants carrying conditionally lethal mutations in outer membrane genes omsA and firA (ssc) are phenotypically similar, and omsA is allelic to firA
Vuorio, R., & Vaara, M. (1992) · Journal of Bacteriology · doi:10.1128/jb.174.22.7090-7097.1992 · Cited by 24 · see citing works
Effect of Ssc protein mutations on the outer membrane permeability barrier function in Salmonella typhimurium: a study using ssc mutant alleles made by site-directed mutagenesis
Hirvas, L. (1992) · FEMS Microbiology Letters · doi:10.1016/0378-1097(92)90662-8 · Cited by 4 · see citing works
Crystallization and preliminary X-ray crystallographic analysis of UDP-N-acetylglucosamine acyltransferase fromHelicobacter pylori
Lee, B. I., Lee, J. Y., Moon, J., Han, B. W., & Suh, S. W. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902004845 · Cited by 4 · see citing works
Effect of Ssc protein mutations on the outer membrane permeability barrier function inSalmonella typhimurium: a study usingsscmutant alleles made by site-directed mutagenesis
Hirvas, L., & Vaara, M. (1992) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1992.tb05168.x · Cited by 2 · see citing works

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Yoshida, N., Emoto, T., Yamashita, T., Watanabe, H., Hayashi, T., Tabata, T., Hoshi, N., Hatano, N., Ozawa, G., Sasaki, N., et al. (2018) · Circulation · doi:10.1161/circulationaha.118.033714 · Cited by 619 · see citing works
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Wang, X., & Quinn, P. J. (2009) · Progress in Lipid Research · doi:10.1016/j.plipres.2009.06.002 · Cited by 472 · see citing works
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Henderson, J. C., Zimmerman, S. M., Crofts, A. A., Boll, J. M., Kuhns, L. G., Herrera, C. M., & Trent, M. S. (2016) · Annual Review of Microbiology · doi:10.1146/annurev-micro-102215-095308 · Cited by 231 · see citing works
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Lung, T. W. F., Giogha, C., Creuzburg, K., Ong, S. Y., Pollock, G. L., Zhang, Y. E., Fung, K. Y., Pearson, J. S., & Hartland, E. L. (2016) · Infection and Immunity · doi:10.1128/iai.01523-15 · Cited by 21 · see citing works
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Ramsden, N. L., Buetow, L., Dawson, A., Kemp, L. E., Ulaganathan, V., Brenk, R., Klebe, G., & Hunter, W. N. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801475n · Cited by 20 · see citing works
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Mindrebo, J. T., Patel, A., Misson, L., Kim, W. E., Davis, T. D., Ni, Q. Z., Clair, J. J. L., & Burkart, M. D. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14662-1 · Cited by 18 · see citing works
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Altınok, İ., Öztürk, R. Ç., Kahraman, U. C., & Çapkın, E. (2016) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2016.04.018 · Cited by 17 · see citing works
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Cai, L., Li, Y., Tao, G., Guo, W., Zhang, C., & Wang, X. (2013) · Marine Drugs · doi:10.3390/md11020377 · Cited by 16 · see citing works
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Kim, S., Yoon, H., & Ryu, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-19306-0 · Cited by 15 · see citing works
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Tsai, C.-Y., Santos, H. M., Hu, S., Sang, C. Y., Yanuaria, C. A. S., Lola, E. N. G., Tayo, L. L., Nitura, K. M. A., Liu, C. H., & Chuang, K. (2019) · Aquaculture International · doi:10.1007/s10499-019-00398-y · Cited by 14 · see citing works
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Badger, J., Chie-Leon, B., Logan, C., Sridhar, V., Sankaran, B., Zwart, P. H., & Nienaber, V. L. (2011) · Acta Crystallographica Section F Structural Biology and Crystallization Communications · doi:10.1107/s1744309111018811 · Cited by 13 · see citing works
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Serral, F., Pardo, A., Sosa, E. J., Palomino, M. M., Nicolas, M. F., Turjanski, A. G., Ramos, P. I. P., & Porto, D. F. D. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.773405 · Cited by 11 · see citing works
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Ahmad, S., Raza, S., Qurat-ul-Ain, Q.-U.-A., Uddin, R., Rungrotmongkol, T., & Azam, S. S. (2018) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2018.06.013 · Cited by 11 · see citing works
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Demendi, M., & Creuzenet, C. (2009) · Biochemistry and Cell Biology · doi:10.1139/o09-002 · Cited by 11 · see citing works
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Rath, S. N., Ray, M., Pattnaik, A., & Pradhan, S. K. (2016) · Genomics & Informatics · doi:10.5808/gi.2016.14.4.241 · Cited by 10 · see citing works
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Yamano, R., Yu, J., Haditomo, A. H. C., Jiang, C., Mino, S., Romalde, J. L., Kang, K., Sakai, Y., & Sawabe, T. (2023) · PLoS ONE · doi:10.1371/journal.pone.0286693 · Cited by 9 · see citing works
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Stead, C. M., Pride, A. C., & Trent, M. S. (2011) · Springer eBooks · doi:10.1007/978-3-7091-0733-1_6 · Cited by 2 · see citing works
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Paquette, S. W. M. (2009) · University of Massachusetts (UMass) Chan Medical School · doi:10.13028/cz1q-z918 · Cited by 1 · see citing works
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Roy, A. (2011) · KU ScholarWorks (The University of Kansas)
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Newmister, S. A., & Sherman, D. H. (2014) · ChemBioChem · doi:10.1002/cbic.201402095
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Belleghem, J. D. V. (2017) · Ghent University Academic Bibliography (Ghent University)
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Schomburg, D., & Schomburg, I. (2013) · Springer eBooks · doi:10.1007/978-3-642-36240-8_40
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Sui, B., Hu, Q., Dingcheng, R., Ding, T., Zhang, Q., Li, L., & Liu, X. (2026) · Nano Energy · doi:10.1016/j.nanoen.2026.112273
BindingDB Entry 3368: A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy.
BindingDB (2009) · UC San Diego · doi:10.7270/q23b5xgb
BindingDB Entry 8018: Structural basis for the recognition of peptide RJPXD33 by acyltransferases in lipid A biosynthesis.
BindingDB (2017) · UC San Diego · doi:10.7270/q2rv0mjp
BindingDB Entry 50020010: Antibacterial activities of anthraquinones: structure-activity relationships and action mechanisms.
BindingDB (2024) · UC San Diego · doi:10.7270/q2pc36t0

Nucleotide Substrate Recognition by UDP-N-acetylglucosamine Acyltransferase (LpxA) in the First Step of Lipid A Biosynthesis
Ulaganathan, V., Buetow, L., & Hunter, W. N. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.03.039 · Cited by 32 · see citing works
Self-citation
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Bartling, C. M., & Raetz, C. R. H. (2009) · Biochemistry · doi:10.1021/bi901025v · Cited by 56 · see citing works
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Lee, B. I., & Suh, S. W. (2003) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10436 · Cited by 24 · see citing works
Structural basis for the acyl chain selectivity and mechanism of UDP- N -acetylglucosamine acyltransferase
Williams, A. H., & Raetz, C. R. H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705833104 · Cited by 84 · see citing works
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Authors: Buetow, L., Smith, T. K., Dawson, A., Fyffe, S., & Hunter, W. N.
Affiliations: University of Dundee (GB)
European Bioinformatics Institute (GB)
Corresponding author: Hunter, William N.
ORCID: Buetow, Lori
Smith, Terry K.
Dawson, Alice
Hunter, William N.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2007-03-13
Volume: 104
Issue: 11
Pages: 4321-4326
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0606356104
PMC: PMC1810333
OpenAlex: W1974604380
Cited by: 78
References: 43
Citations by year: 2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 2 · 2019: 6 · 2018: 5 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 7 · 2013: 5 · 2012: 4
FWCI: 3.50
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (publishedVersion)
Funders: Wellcome Trust
European Synchrotron Radiation Facility
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council
Topics: Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
Keywords: N-acyltransferase, lipid A biosynthesis, lipopolysaccharide biosynthesis, Chlamydia trachomatis, acyl carrier protein, lipid-binding domain, catalytic mechanism, fatty acid binding, palmitic acid, nucleotide binding, Gram-negative bacterial outer membrane
MeSH terms: Acyltransferases, Amino Acid Sequence, Carbon, Chlamydia trachomatis, Cloning, Molecular, Fatty Acids, Hydrogen Bonding, Lipid A, Models, Chemical, Models, Molecular, Molecular Sequence Data, Mass Spectrometry, Uridine Diphosphate N-Acetylglucosamine, Crystallography, X-Ray

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Structure and reactivity of LpxD, the N -acyltransferase of lipid A biosynthesis

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