skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
DOE - BASIC ENERGY SCIENCES
OSTI Identifier:
1577158
Resource Type:
Journal Article
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Kroeck, Kyle G., Sacco, Michael D., Smith, Emmanuel W., Zhang, Xiujun, Shoun, Daniel, Akhtar, Afroza, Darch, Sophie E., Cohen, Frederick, Andrews, Logan D., Knox, John E., and Chen, Yu. Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography. United States: N. p., 2019. Web. doi:10.1038/s41598-019-51844-z.
Kroeck, Kyle G., Sacco, Michael D., Smith, Emmanuel W., Zhang, Xiujun, Shoun, Daniel, Akhtar, Afroza, Darch, Sophie E., Cohen, Frederick, Andrews, Logan D., Knox, John E., & Chen, Yu. Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography. United States. doi:10.1038/s41598-019-51844-z.
Kroeck, Kyle G., Sacco, Michael D., Smith, Emmanuel W., Zhang, Xiujun, Shoun, Daniel, Akhtar, Afroza, Darch, Sophie E., Cohen, Frederick, Andrews, Logan D., Knox, John E., and Chen, Yu. Tue . "Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography". United States. doi:10.1038/s41598-019-51844-z.
@article{osti_1577158,
title = {Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography},
author = {Kroeck, Kyle G. and Sacco, Michael D. and Smith, Emmanuel W. and Zhang, Xiujun and Shoun, Daniel and Akhtar, Afroza and Darch, Sophie E. and Cohen, Frederick and Andrews, Logan D. and Knox, John E. and Chen, Yu},
abstractNote = {},
doi = {10.1038/s41598-019-51844-z},
journal = {Scientific Reports},
issn = {2045-2322},
number = 1,
volume = 9,
place = {United States},
year = {2019},
month = {10}
}

Works referenced in this record:

The Active Site of Escherichia coli UDP- N -acetylglucosamine Acyltransferase : CHEMICAL MODIFICATION AND SITE-DIRECTED MUTAGENESIS
journal, September 1999

  • Wyckoff, Timna J. O.; Raetz, Christian R. H.
  • Journal of Biological Chemistry, Vol. 274, Issue 38
  • DOI: 10.1074/jbc.274.38.27047

Multi-targeting by monotherapeutic antibacterials
journal, January 2007

  • Silver, Lynn L.
  • Nature Reviews Drug Discovery, Vol. 6, Issue 1
  • DOI: 10.1038/nrd2202

Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

Chasing acyl carrier protein through a catalytic cycle of lipid A production
journal, November 2013

  • Masoudi, Ali; Raetz, Christian R. H.; Zhou, Pei
  • Nature, Vol. 505, Issue 7483
  • DOI: 10.1038/nature12679

Active-Site Druggability of Carbapenemases and Broad-Spectrum Inhibitor Discovery
journal, April 2019


Structural Basis for the Recognition of Peptide RJPXD33 by Acyltransferases in Lipid A Biosynthesis
journal, April 2014

  • Jenkins, Ronald J.; Heslip, Kyle A.; Meagher, Jennifer L.
  • Journal of Biological Chemistry, Vol. 289, Issue 22
  • DOI: 10.1074/jbc.M114.564278

A High-Throughput–Compatible Fluorescence Anisotropy-Based Assay for Competitive Inhibitors of Escherichia coli UDP- N -Acetylglucosamine Acyltransferase (LpxA)
journal, March 2013

  • Shapiro, Adam B.; Ross, Philip L.; Gao, Ning
  • Journal of Biomolecular Screening, Vol. 18, Issue 3
  • DOI: 10.1177/1087057112462062

Structure guided design of an antibacterial peptide that targets UDP-N-acetylglucosamine acyltransferase
journal, March 2019

  • Dangkulwanich, Manchuta; Raetz, Christian R. H.; Williams, Allison H.
  • Scientific Reports, Vol. 9, Issue 1
  • DOI: 10.1038/s41598-019-40418-8

Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2)
journal, April 2017


Steady-State Kinetics and Mechanism of LpxD, the N -Acyltransferase of Lipid A Biosynthesis
journal, May 2008

  • Bartling, Craig M.; Raetz, Christian R. H.
  • Biochemistry, Vol. 47, Issue 19
  • DOI: 10.1021/bi800240r

The novel hexapeptide motif found in the acyltransferases LpxA and LpxD of lipid A biosynthesis is conserved in various bacteria
journal, January 1994


The structure of LpxD from Pseudomonas aeruginosa at 1.3 Å resolution
journal, June 2011

  • Badger, John; Chie-Leon, Barbara; Logan, Cheyenne
  • Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 67, Issue 7
  • DOI: 10.1107/S1744309111018811

Review: Lipopolysaccharide biosynthesis in Pseudomonas aeruginosa
journal, August 2009


Molecular docking and ligand specificity in fragment-based inhibitor discovery
journal, March 2009


Structures of Bacteroides fragilis uridine 5′-diphosphate- N -acetylglucosamine (UDP-GlcNAc) acyltransferase (BfLpxA)
journal, April 2015

  • Ngo, Alice; Fong, Kai T.; Cox, Daniel L.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 5
  • DOI: 10.1107/S1399004715003326

A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening
journal, April 2002

  • McGovern, Susan L.; Caselli, Emilia; Grigorieff, Nikolaus
  • Journal of Medicinal Chemistry, Vol. 45, Issue 8
  • DOI: 10.1021/jm010533y

On the essentiality of lipopolysaccharide to Gram-negative bacteria
journal, December 2013

  • Zhang, Ge; Meredith, Timothy C.; Kahne, Daniel
  • Current Opinion in Microbiology, Vol. 16, Issue 6
  • DOI: 10.1016/j.mib.2013.09.007

A Left-Handed Parallel beta Helix in the Structure of UDP-N-Acetylglucosamine Acyltransferase
journal, November 1995


Antibacterial Agents That Target Lipid A Biosynthesis in Gram-negative Bacteria: INHIBITION OF DIVERSE UDP-3-
journal, April 2000

  • Jackman, Jane E.; Fierke, Carol A.; Tumey, L. Nathan
  • Journal of Biological Chemistry, Vol. 275, Issue 15
  • DOI: 10.1074/jbc.275.15.11002

Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase
journal, August 2007

  • Williams, A. H.; Raetz, C. R. H.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 34
  • DOI: 10.1073/pnas.0705833104

Lipopolysaccharide Endotoxins
journal, June 2002


Biosynthesis and Export of Bacterial Lipopolysaccharides
journal, June 2014



journal, August 2005


Crystal Structure and Acyl Chain Selectivity of Escherichia coli LpxD, the N -Acyltransferase of Lipid A Biosynthesis
journal, September 2009

  • Bartling, Craig M.; Raetz, Christian R. H.
  • Biochemistry, Vol. 48, Issue 36
  • DOI: 10.1021/bi901025v

Antibacterial Spectrum of a Tetrazole-Based Reversible Inhibitor of Serine β-Lactamases
journal, May 2018

  • Pemberton, Orville A.; Zhang, Xiujun; Nichols, Derek A.
  • Antimicrobial Agents and Chemotherapy, Vol. 62, Issue 8
  • DOI: 10.1128/AAC.02563-17

Lipid A as a Drug Target and Therapeutic Molecule
journal, November 2015


Structure determination of LpxD from the lipopolysaccharide-synthesis pathway of Acinetobacter baumannii
journal, December 2012

  • Badger, John; Chie-Leon, Barbara; Logan, Cheyenne
  • Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 69, Issue 1
  • DOI: 10.1107/S1744309112048890

An Aggregation Advisor for Ligand Discovery
journal, August 2015


Activity and Crystal Structure of Arabidopsis thaliana UDP- N -Acetylglucosamine Acyltransferase
journal, May 2012

  • Joo, Sang Hoon; Chung, Hak Suk; Raetz, Christian R. H.
  • Biochemistry, Vol. 51, Issue 21
  • DOI: 10.1021/bi3002242

Antibacterial Agents That Inhibit Lipid A Biosynthesis
journal, November 1996


Kdo 2 -lipid A: structural diversity and impact on immunopharmacology : Kdo
journal, May 2014

  • Wang, Xiaoyuan; Quinn, Peter J.; Yan, Aixin
  • Biological Reviews, Vol. 90, Issue 2
  • DOI: 10.1111/brv.12114

Endotoxemia in Human Septic Shock
journal, January 1991

  • Danner, Robert L.; Elin, Ronald J.; Hosseini, Jeanette M.
  • Chest, Vol. 99, Issue 1
  • DOI: 10.1378/chest.99.1.169

LpxC inhibitors: a patent review (2010-2016)
journal, July 2017


Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity
journal, September 2015



journal, February 2008


Structure and reactivity of LpxD, the N-acyltransferase of lipid A biosynthesis
journal, March 2007

  • Buetow, L.; Smith, T. K.; Dawson, A.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 11
  • DOI: 10.1073/pnas.0606356104

Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide
journal, July 2006

  • Williams, A. H.; Immormino, R. M.; Gewirth, D. T.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 29
  • DOI: 10.1073/pnas.0604465103

Structure determination of LpxA from the lipopolysaccharide-synthesis pathway of Acinetobacter baumannii
journal, November 2012

  • Badger, John; Chie-Leon, Barbara; Logan, Cheyenne
  • Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 68, Issue 12
  • DOI: 10.1107/S174430911204571X

Dual Targeting Antibacterial Peptide Inhibitor of Early Lipid A Biosynthesis
journal, April 2012

  • Jenkins, Ronald J.; Dotson, Garry D.
  • ACS Chemical Biology, Vol. 7, Issue 7
  • DOI: 10.1021/cb300094a

Nucleotide Substrate Recognition by UDP-N-acetylglucosamine Acyltransferase (LpxA) in the First Step of Lipid A Biosynthesis
journal, June 2007

  • Ulaganathan, Venkatasubramanian; Buetow, Lori; Hunter, William N.
  • Journal of Molecular Biology, Vol. 369, Issue 2
  • DOI: 10.1016/j.jmb.2007.03.039