5FGN

Integral membrane protein lipooligosaccharide phosphoethanolamine transferase A (EptA) from Neisseria meningitidis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.215 

Starting Model: experimental
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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted LMTClick on this verticalbar to view detailsBest fitted BGLClick on this verticalbar to view details

This is version 1.7 of the entry. See complete history


Literature

Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding.

Anandan, A.Evans, G.L.Condic-Jurkic, K.O'Mara, M.L.John, C.M.Phillips, N.J.Jarvis, G.A.Wills, S.S.Stubbs, K.A.Moraes, I.Kahler, C.M.Vrielink, A.

(2017) Proc Natl Acad Sci U S A 114: 2218-2223

  • DOI: https://doi.org/10.1073/pnas.1612927114
  • Primary Citation of Related Structures:  
    5FGN

  • PubMed Abstract: 

    Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4' headgroup positions by phosphoethanolamine transferases. Previous structural work on a truncated form of this enzyme suggested that the full-length protein was required for correct lipid substrate binding and catalysis. We now report the crystal structure of a full-length lipid A phosphoethanolamine transferase from Neisseria meningitidis , determined to 2.75-Å resolution. The structure reveals a previously uncharacterized helical membrane domain and a periplasmic facing soluble domain. The domains are linked by a helix that runs along the membrane surface interacting with the phospholipid head groups. Two helices located in a periplasmic loop between two transmembrane helices contain conserved charged residues and are implicated in substrate binding. Intrinsic fluorescence, limited proteolysis, and molecular dynamics studies suggest the protein may sample different conformational states to enable the binding of two very different- sized lipid substrates. These results provide insights into the mechanism of endotoxin modification and will aid a structure-guided rational drug design approach to treating multidrug-resistant bacterial infections.


  • Organizational Affiliation

    School of Molecular Sciences, University of Western Australia, Crawley, WA 6009, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
lipooligosaccharide phosphoethanolamine transferase A550Neisseria meningitidis serogroup BMutation(s): 0 
Gene Names: NMB1638
Membrane Entity: Yes 
UniProt
Find proteins for Q7DD94 (Neisseria meningitidis serogroup B (strain ATCC BAA-335 / MC58))
Explore Q7DD94 
Go to UniProtKB:  Q7DD94
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ7DD94
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.215 
  • Space Group: I 4 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 187.285α = 90
b = 187.285β = 90
c = 205.125γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted LMTClick on this verticalbar to view detailsBest fitted BGLClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)AustraliaAPP 1003697
National Health and Medical Research Council (NHMRC, Australia)AustraliaAPP 1078642

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-15
    Type: Initial release
  • Version 1.1: 2017-03-01
    Changes: Database references
  • Version 1.2: 2017-03-08
    Changes: Database references
  • Version 1.3: 2017-09-27
    Changes: Author supporting evidence, Data collection
  • Version 1.4: 2020-01-08
    Changes: Author supporting evidence
  • Version 1.5: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.6: 2023-09-27
    Changes: Data collection, Database references, Refinement description, Structure summary
  • Version 1.7: 2024-11-06
    Changes: Structure summary