4Q9I

P-glycoprotein cocrystallised with QZ-Ala


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.78 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.263 
  • R-Value Observed: 0.265 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Snapshots of ligand entry, malleable binding and induced helical movement in P-glycoprotein.

Szewczyk, P.Tao, H.McGrath, A.P.Villaluz, M.Rees, S.D.Lee, S.C.Doshi, R.Urbatsch, I.L.Zhang, Q.Chang, G.

(2015) Acta Crystallogr D Biol Crystallogr 71: 732-741

  • DOI: https://doi.org/10.1107/S1399004715000978
  • Primary Citation of Related Structures:  
    4Q9H, 4Q9I, 4Q9J, 4Q9K, 4Q9L

  • PubMed Abstract: 

    P-glycoprotein (P-gp) is a transporter of great clinical and pharmacological significance. Several structural studies of P-gp and its homologs have provided insights into its transport cycle, but questions remain regarding how P-gp recognizes diverse substrates and how substrate binding is coupled to ATP hydrolysis. Here, four new P-gp co-crystal structures with a series of rationally designed ligands are presented. It is observed that the binding of certain ligands, including an ATP-hydrolysis stimulator, produces a large conformational change in the fourth transmembrane helix, which is positioned to potentially transmit a signal to the nucleotide-binding domains. A new ligand-binding site on the surface of P-gp facing the inner leaflet of the membrane is also described, providing vital insights regarding the entry mechanism of hydrophobic drugs and lipids into P-gp. These results represent significant advances in the understanding of how P-gp and related transporters bind and export a plethora of metabolites, antibiotics and clinically approved and pipeline drugs.


  • Organizational Affiliation

    Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92023, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Multidrug resistance protein 1A1,284Mus musculusMutation(s): 0 
Gene Names: Abcb1aAbcb4Mdr1aMdr3Pgy-3Pgy3
EC: 3.6.3.44
Membrane Entity: Yes 
UniProt
Find proteins for P21447 (Mus musculus)
Explore P21447 
Go to UniProtKB:  P21447
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP21447
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
(30F)A(30F)A(30F)A Peptide
B, C
6N/AMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
30F
Query on 30F
B, C
PEPTIDE LINKINGC3 H5 N O2 SeSEC
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.78 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.263 
  • R-Value Observed: 0.265 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.642α = 90
b = 138.398β = 90
c = 183.712γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-04
    Type: Initial release
  • Version 1.1: 2015-03-18
    Changes: Database references
  • Version 1.2: 2016-05-25
    Changes: Structure summary
  • Version 2.0: 2023-11-15
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations