4J09

Crystal Structure of LpxA bound to RJPXD33


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.177 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.172 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural Basis for the Recognition of Peptide RJPXD33 by Acyltransferases in Lipid A Biosynthesis.

Jenkins, R.J.Heslip, K.A.Meagher, J.L.Stuckey, J.A.Dotson, G.D.

(2014) J Biol Chem 289: 15527-15535

  • DOI: https://doi.org/10.1074/jbc.M114.564278
  • Primary Citation of Related Structures:  
    4J09

  • PubMed Abstract: 

    UDP-N-acetylglucosamine acyltransferase (LpxA) and UDP-3-O-(acyl)-glucosamine acyltransferase (LpxD) constitute the essential, early acyltransferases of lipid A biosynthesis. Recently, an antimicrobial peptide inhibitor, RJPXD33, was identified with dual affinity for LpxA and LpxD. To gain a fundamental understanding of the molecular basis of inhibitor binding, we determined the crystal structure of LpxA from Escherichia coli in complex with RJPXD33 at 1.9 Å resolutions. Our results suggest that the peptide binds in a unique modality that mimics (R)-β-hydroxyacyl pantetheine binding to LpxA and displays how the peptide binds exclusive of the native substrate, acyl-acyl carrier protein. Acyltransferase binding studies with photo-labile RJPXD33 probes and truncations of RJPXD33 validated the structure and provided fundamental insights for future design of small molecule inhibitors. Overlay of the LpxA-RJPXD33 structure with E. coli LpxD identified a complementary peptide binding pocket within LpxD and serves as a model for further biochemical characterization of RJPXD33 binding to LpxD.


  • Organizational Affiliation

    From the Department of Medicinal Chemistry, College of Pharmacy, and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase262Escherichia coli K-12Mutation(s): 0 
Gene Names: b0181JW0176lpxA
EC: 2.3.1.129
UniProt
Find proteins for P0A722 (Escherichia coli (strain K12))
Explore P0A722 
Go to UniProtKB:  P0A722
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0A722
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Putative metabolite transport protein YjhB6Escherichia coli K-12Mutation(s): 0 
UniProt
Find proteins for P39352 (Escherichia coli (strain K12))
Explore P39352 
Go to UniProtKB:  P39352
Entity Groups  
UniProt GroupP39352
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.177 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.172 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 96.399α = 90
b = 96.399β = 90
c = 96.399γ = 90
Software Package:
Software NamePurpose
PHASERphasing
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
BUSTERrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-04-23
    Type: Initial release
  • Version 1.1: 2014-06-11
    Changes: Database references
  • Version 1.2: 2014-06-18
    Changes: Database references
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations