New GPCR structures - CXCR4 now available from PDBe

27 Oct 2010

The newly published CXCR4 ligand complex structures are now released in PDBe. In total there are 5 new PDB entries (3odu, 3oe0, 3oe6, 3oe8 and 3oe9) but 9 distinct new chain structures (some PDB entries have multiple copies of CXCR4 in the asymmetric unit). All structures are complexed with a ligand, either a small molecule antagonist, called IT1t (pictured below), or a medium sized peptide antagonist, CVX-15 (Arg-Arg-Nal-Cys-Tyr-Gln-Lys-dPro-Pro-Tyr-Arg-Cit-Cys-Arg-Gly-dPro).

Interested readers are also directed to an excellent blog http://emeraldbiostructures.com/gpcrblog/ with a deep focus on structural biology, protein chemistry, engineering of GPCRs. There are reported to be several more GPCR structures currently solved, including S1P and D2.

Here is a table of the new structures from PDBe. The GPCR structure table has been updated (but you will probably need to download this in order to make sense of it).

3oe9 view	Crystal structure of the chemokine CXCR4 receptor in complex with a small molecule antagonist IT1t in P1 spacegroup	x-ray diffraction	3.1	2010/10/27
3oe0 view	Crystal structure of the CXCR4 chemokine receptor in complex with a cyclic peptide antagonist CVX15	x-ray diffraction	2.9	2010/10/27
3oe6 view	Crystal structure of the CXCR4 chemokine receptor in complex with a small molecule antagonist IT1t in I222 spacegroup	x-ray diffraction	3.2	2010/10/27
3oe8 view	Crystal structure of the CXCR4 chemokine receptor in complex with a small molecule antagonist IT1t in P1 spacegroup	x-ray diffraction	3.1	2010/10/27
3odu view	The 2.5 A structure of the CXCR4 chemokine receptor in complex with small molecule antagonist IT1t	x-ray diffraction	2.5	2010/10/27

Fitting all these CXCR4 structures together, gives 239 equivalenced Calpha atoms (using an equivalence cutoff of 4.5Angstrom). The processing of the files for the fit included removal of the lysozyme insert domain and also any extraneous ligands and waters. When MDS is performed on the RMSD matrix, the major determinant of the structural similarity is the bound ligand, (not surprisingly given the difference in size of IT1t and CVX-15).

Here are the overlaid coordinates. 3oduA, 3oduB, 3oe0A, 3oe6A, 3oe8A, 3oe8B, 3oe8C, 3oe9A, 3oe9B. As noted above, the coordinate sets have been substantially edited compared to the original PDB entries.

Below is the joy formatted sequence of 3oduA - lower case=non-core, UPPER case=core, red=helix, blue=sheet, italic=positive phi.

pçfreenanfnkiflptiYsiIfltGivgNglvilvMgyqkklrsmtdkY
RlhLSvADllFVitLpfWavDAvanWyfgnflÇkaVHviYTVNlYSSVwI
LAfISlDRylAiVhatnsqrprkllAekvVyvgVwipAlllTipDfifAn
vseaddryiÇdrfypndlwvvvfqfqhimvglilPgivIlsCyciIiskl
shs kghqkrkalktTviLilaFfacWlpyyigisidsfilleiikqgçe
fentvhkwisitEAlAFfHCclNpilyaflgakfktsaqhalts

%T Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists
%J Science
%D 2010
%V 330
%A B. Wu
%A E.Y.T. Chien
%A C.D. Mol
%A G. Fenalti
%A W. Liu 
%A V. Katritch
%A R. Abagyan
%A A. Brooun
%A P. Wells
%A F.C. Bi
%A D.J. Hamel
%A P. Kuhn
%A T.M. Handel
%A V. Cherezov
%A R.C. Stevens
%O DOI: 10.1126/science.1194396

(PDBe

On the 3rd November, the structure of human D3 receptor complexed with Eticlopride was released (PDBe:3pbl)