3ODU

The 2.5 A structure of the CXCR4 chemokine receptor in complex with small molecule antagonist IT1t


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.237 
  • R-Value Observed: 0.240 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists.

Wu, B.Chien, E.Y.Mol, C.D.Fenalti, G.Liu, W.Katritch, V.Abagyan, R.Brooun, A.Wells, P.Bi, F.C.Hamel, D.J.Kuhn, P.Handel, T.M.Cherezov, V.Stevens, R.C.

(2010) Science 330: 1066-1071

  • DOI: https://doi.org/10.1126/science.1194396
  • Primary Citation of Related Structures:  
    3ODU, 3OE0, 3OE6, 3OE8, 3OE9

  • PubMed Abstract: 

    Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation, and development. The G protein-coupled chemokine receptor CXCR4 is specifically implicated in cancer metastasis and HIV-1 infection. Here we report five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5 to 3.2 angstrom resolution. All structures reveal a consistent homodimer with an interface including helices V and VI that may be involved in regulating signaling. The location and shape of the ligand-binding sites differ from other G protein-coupled receptors and are closer to the extracellular surface. These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12, and with the HIV-1 glycoprotein gp120.


  • Organizational Affiliation

    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
C-X-C chemokine receptor type 4, Lysozyme Chimera
A, B
502Homo sapiensTequatrovirus T4Mutation(s): 3 
Gene Names: CXCR4CXCR4_HUMANE
EC: 3.2.1.17
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P61073 (Homo sapiens)
Explore P61073 
Go to UniProtKB:  P61073
PHAROS:  P61073
GTEx:  ENSG00000121966 
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP00720P61073
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ITD
Query on ITD

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
(6,6-dimethyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-3-yl)methyl N,N'-dicyclohexylimidothiocarbamate
C21 H34 N4 S2
OOSUDWRRWZVFEB-UHFFFAOYSA-N
OLC
Query on OLC

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
I [auth B],
J [auth B]
(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
C21 H40 O4
RZRNAYUHWVFMIP-GDCKJWNLSA-N
OLA
Query on OLA

Download Ideal Coordinates CCD File 
G [auth A]
K [auth B]
L [auth B]
M [auth B]
N [auth B]
G [auth A],
K [auth B],
L [auth B],
M [auth B],
N [auth B],
O [auth B]
OLEIC ACID
C18 H34 O2
ZQPPMHVWECSIRJ-KTKRTIGZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ITD PDBBind:  3ODU Ki: 7.3 (nM) from 1 assay(s)
BindingDB:  3ODU IC50: min: 1.1, max: 7400 (nM) from 14 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.237 
  • R-Value Observed: 0.240 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.54α = 90
b = 83.692β = 102.17
c = 119.995γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2010-10-27
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-05-02
    Changes: Structure summary
  • Version 1.3: 2017-07-26
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2021-10-06
    Changes: Database references, Derived calculations