3WME

Crystal structure of an inward-facing eukaryotic ABC multidrug transporter


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.212 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog.

Kodan, A.Yamaguchi, T.Nakatsu, T.Sakiyama, K.Hipolito, C.J.Fujioka, A.Hirokane, R.Ikeguchi, K.Watanabe, B.Hiratake, J.Kimura, Y.Suga, H.Ueda, K.Kato, H.

(2014) Proc Natl Acad Sci U S A 111: 4049-4054

  • DOI: https://doi.org/10.1073/pnas.1321562111
  • Primary Citation of Related Structures:  
    3WME, 3WMF, 3WMG

  • PubMed Abstract: 

    P-glycoprotein is an ATP-binding cassette multidrug transporter that actively transports chemically diverse substrates across the lipid bilayer. The precise molecular mechanism underlying transport is not fully understood. Here, we present crystal structures of a eukaryotic P-glycoprotein homolog, CmABCB1 from Cyanidioschyzon merolae, in two forms: unbound at 2.6-Å resolution and bound to a unique allosteric inhibitor at 2.4-Å resolution. The inhibitor clamps the transmembrane helices from the outside, fixing the CmABCB1 structure in an inward-open conformation similar to the unbound structure, confirming that an outward-opening motion is required for ATP hydrolysis cycle. These structures, along with site-directed mutagenesis and transporter activity measurements, reveal the detailed architecture of the transporter, including a gate that opens to extracellular side and two gates that open to intramembranous region and the cytosolic side. We propose that the motion of the nucleotide-binding domain drives those gating apparatuses via two short intracellular helices, IH1 and IH2, and two transmembrane helices, TM2 and TM5.


  • Organizational Affiliation

    Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ATP-binding cassette, sub-family B, member 1612Cyanidioschyzon merolae strain 10DMutation(s): 0 
Gene Names: CMD148CCYME_CMD148C
Membrane Entity: Yes 
UniProt
Find proteins for M1VAN7 (Cyanidioschyzon merolae (strain NIES-3377 / 10D))
Explore M1VAN7 
Go to UniProtKB:  M1VAN7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupM1VAN7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DMU
Query on DMU

Download Ideal Coordinates CCD File 
B [auth A]DECYL-BETA-D-MALTOPYRANOSIDE
C22 H42 O11
WOQQAWHSKSSAGF-WXFJLFHKSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.212 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 180.312α = 90
b = 180.312β = 90
c = 152.332γ = 120
Software Package:
Software NamePurpose
SCALEPACKdata scaling
SOLVEphasing
RESOLVEphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
PHENIXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-03-19
    Type: Initial release
  • Version 1.1: 2016-09-07
    Changes: Database references, Source and taxonomy
  • Version 1.2: 2017-11-22
    Changes: Refinement description
  • Version 1.3: 2024-03-20
    Changes: Data collection, Database references, Derived calculations