5KO2

Mouse pgp 34 linker deleted mutant Hg derivative


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.243 
  • R-Value Observed: 0.244 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity.

Esser, L.Zhou, F.Pluchino, K.M.Shiloach, J.Ma, J.Tang, W.K.Gutierrez, C.Zhang, A.Shukla, S.Madigan, J.P.Zhou, T.Kwong, P.D.Ambudkar, S.V.Gottesman, M.M.Xia, D.

(2017) J Biol Chem 292: 446-461

  • DOI: https://doi.org/10.1074/jbc.M116.755884
  • Primary Citation of Related Structures:  
    5KO2, 5KOY, 5KPD, 5KPI, 5KPJ

  • PubMed Abstract: 

    P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancer; it plays important roles in determining the pharmacokinetics of many drugs. Understanding the structural basis of P-gp, substrate polyspecificity has been hampered by its intrinsic flexibility, which is facilitated by a 75-residue linker that connects the two halves of P-gp. Here we constructed a mutant murine P-gp with a shortened linker to facilitate structural determination. Despite dramatic reduction in rhodamine 123 and calcein-AM transport, the linker-shortened mutant P-gp possesses basal ATPase activity and binds ATP only in its N-terminal nucleotide-binding domain. Nine independently determined structures of wild type, the linker mutant, and a methylated P-gp at up to 3.3 Å resolution display significant movements of individual transmembrane domain helices, which correlated with the opening and closing motion of the two halves of P-gp. The open-and-close motion alters the surface topology of P-gp within the drug-binding pocket, providing a mechanistic explanation for the polyspecificity of P-gp in substrate interactions.


  • Organizational Affiliation

    From the Laboratory of Cell Biology, Center for Cancer Research, NCI.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Multidrug resistance protein 1A
A, B
1,248Mus musculusMutation(s): 2 
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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HG
Query on HG

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth B],
K [auth B],
L [auth B],
M [auth B],
N [auth B],
O [auth B],
P [auth B]
MERCURY (II) ION
Hg
BQPIGGFYSBELGY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.243 
  • R-Value Observed: 0.244 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.185α = 90
b = 114.741β = 90
c = 375.431γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
SCALEPACKdata scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
SHARPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-30
    Type: Initial release
  • Version 1.1: 2016-12-21
    Changes: Database references
  • Version 1.2: 2017-01-25
    Changes: Data collection, Database references
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Refinement description