6T1Z

LmrP from L. lactis, in an outward-open conformation, bound to Hoechst 33342


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity.

Debruycker, V.Hutchin, A.Masureel, M.Ficici, E.Martens, C.Legrand, P.Stein, R.A.Mchaourab, H.S.Faraldo-Gomez, J.D.Remaut, H.Govaerts, C.

(2020) Nat Struct Mol Biol 27: 829-835

  • DOI: https://doi.org/10.1038/s41594-020-0464-y
  • Primary Citation of Related Structures:  
    6T1Z

  • PubMed Abstract: 

    Multidrug efflux pumps present a challenge to the treatment of bacterial infections, making it vitally important to understand their mechanism of action. Here, we investigate the nature of substrate binding within Lactococcus lactis LmrP, a prototypical multidrug transporter of the major facilitator superfamily. We determined the crystal structure of LmrP in a ligand-bound outward-open state and observed an embedded lipid in the binding cavity of LmrP, an observation supported by native mass spectrometry analyses. Molecular dynamics simulations suggest that the anionic lipid stabilizes the observed ligand-bound structure. Mutants engineered to disrupt binding of the embedded lipid display reduced transport of some, but not all, antibiotic substrates. Our results suggest that a lipid within the binding cavity could provide a malleable hydrophobic component that allows adaptation to the presence of different substrates, helping to explain the broad specificity of this protein and possibly other multidrug transporters.


  • Organizational Affiliation

    Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
LmrP integral membrane protein411Lactococcus lactisMutation(s): 0 
Gene Names: lmrP
Membrane Entity: Yes 
UniProt
Find proteins for Q48658 (Lactococcus lactis)
Explore Q48658 
Go to UniProtKB:  Q48658
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ48658
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
XP4 (Subject of Investigation/LOI)
Query on XP4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHATE
C31 H60 O8 P
OZSITQMWYBNPMW-GDLZYMKVSA-M
LMU
Query on LMU

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A]
DODECYL-ALPHA-D-MALTOSIDE
C24 H46 O11
NLEBIOOXCVAHBD-YHBSTRCHSA-N
HT1 (Subject of Investigation/LOI)
Query on HT1

Download Ideal Coordinates CCD File 
B [auth A]2'-(4-ETHOXYPHENYL)-5-(4-METHYL-1-PIPERAZINYL)-2,5'-BI-BENZIMIDAZOLE
C27 H28 N6 O
PRDFBSVERLRRMY-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.225 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.76α = 90
b = 139.99β = 90
c = 115.7γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
XSCALEdata scaling
Aimlessdata scaling
STARANISOdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-07-29
    Type: Initial release
  • Version 1.1: 2020-08-05
    Changes: Database references
  • Version 1.2: 2020-09-16
    Changes: Database references
  • Version 1.3: 2021-02-10
    Changes: Database references