PDBsum entry: 3eml

Membrane protein, receptor

PDB-id

3eml


	Main view

Contents

Description

Header details

Protein chain

Ligands

ZMA

STE ×5

SO4 ×7

Waters ×76

* Residue conservation analysis

Tools

Image Generation

AstexViewer™@PDBe

Run PROCHECK

Clefts Calculation


Bottom view		Right view

PDB id:

3eml

Name:

Membrane protein, receptor

Title:

The 2.6 a crystal structure of a human a2a adenosine receptor bound to zm241385.

Structure:

Human adenosine a2a receptor/t4 lysozyme chimera. Chain: a. Engineered: yes

Source:

Homo sapiens, enterobacteria phage t4, homo sapiens. Organism_taxid: 9606, 10665, 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

UniProt:

P29274 (AA2AR_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

412 a.a.

Struc:

448 a.a.*

Key:

PfamA domain

Secondary structure

* PDB and UniProt seqs differ at 152 residue positions (black crosses)

Resolution:

2.60Å

R-factor:

0.198

R-free:

0.231

Authors:

V.-P.Jaakola,M.T.Griffith,M.A.Hanson,V.Cherezov,E.Y.T.Chien, J.R.Lane,A.P.Ijzerman,R.C.Stevens,Accelerated Technologies Center For Gene To 3d Structure (Atcg3d)

Key ref:

V.P.Jaakola et al. (2008). The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist.. Science, 322, 1211-1217. [PubMed id: 18832607] [DOI: 10.1126/science.1164772]

Date:

24-Sep-08

Release date:

14-Oct-08

Quick_links

RCSB

PDBe

SRS

MMDB

JenaLib

OCA

Proteopedia

CATH

SCOP

FSSP

HSSP

PDBSWS

OPM

PQS

CSA

ProSAT

Whatcheck

EDS

Procheck

Clefts

Surface

Key reference

DOI no: 10.1126/science.1164772 Science 322:1211-1217 (2008)

PubMed id: 18832607

The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist.

V.P.Jaakola, M.T.Griffith, M.A.Hanson, V.Cherezov, E.Y.Chien, J.R.Lane, A.P.Ijzerman, R.C.Stevens.

ABSTRACT

The adenosine class of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) mediates the important role of extracellular adenosine in many physiological processes and is antagonized by caffeine. We have determined the crystal structure of the human A(2A) adenosine receptor, in complex with a high-affinity subtype-selective antagonist, ZM241385, to 2.6 angstrom resolution. Four disulfide bridges in the extracellular domain, combined with a subtle repacking of the transmembrane helices relative to the adrenergic and rhodopsin receptor structures, define a pocket distinct from that of other structurally determined GPCRs. The arrangement allows for the binding of the antagonist in an extended conformation, perpendicular to the membrane plane. The binding site highlights an integral role for the extracellular loops, together with the helical core, in ligand recognition by this class of GPCRs and suggests a role for ZM241385 in restricting the movement of a tryptophan residue important in the activation mechanism of the class A receptors.

Literature references that cite this PDB file's key reference

PubMed id Reference

19458711 D.M.Rosenbaum, S.G.Rasmussen, and B.K.Kobilka (2009).
The structure and function of G-protein-coupled receptors.

Nature, 459, 356-363.

19339946 D.T.Lodowski, and K.Palczewski (2009).
Chemokine receptors and other G protein-coupled receptors.

Curr Opin HIV AIDS, 4, 88-95.

19192200 D.T.Lodowski, T.E.Angel, and K.Palczewski (2009).
Comparative Analysis of GPCR Crystal Structures.

Photochem Photobiol, 85, 425-430.

19339947 G.Alkhatib (2009).
The biology of CCR5 and CXCR4.

Curr Opin HIV AIDS, 4, 96.

19190775 H.J.Atkinson, J.H.Morris, T.E.Ferrin, and P.C.Babbitt (2009).
Using sequence similarity networks for visualization of relationships across diverse protein superfamilies.

PLoS ONE, 4, e4345.

19466696 J.Lättig, A.Oksche, M.Beyermann, W.Rosenthal, and G.Krause (2009).
Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETA and ETB.

J Pept Sci, 15, 479-491.

19390528 M.Caffrey, and V.Cherezov (2009).
Crystallizing membrane proteins using lipidic mesophases.

Nat Protoc, 4, 706-731.

19581583 M.M.Torrice, K.S.Bower, H.A.Lester, and D.A.Dougherty (2009).
Probing the role of the cation-pi interaction in the binding sites of GPCRs using unnatural amino acids.

Proc Natl Acad Sci U S A, 106, 11919-11924.

19461661 M.Michino, E.Abola, C.L.Brooks, J.S.Dixon, J.Moult, and R.C.Stevens (2009).
Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008.

Nat Rev Drug Discov, 8, 455-463.

19389717 P.Milovnik, D.Ferrari, C.A.Sarkar, and A.Plückthun (2009).
Selection and characterization of DARPins specific for the neurotensin receptor 1.

Protein Eng Des Sel, 22, 357-366.

19258456 R.O.Dror, D.H.Arlow, D.W.Borhani, M.�.�.Jensen, S.Piana, and D.E.Shaw (2009).
Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations.

Proc Natl Acad Sci U S A, 106, 4689-4694.

19343763 R.Volpini, D.Dal Ben, C.Lambertucci, G.Marucci, R.C.Mishra, A.T.Ramadori, K.N.Klotz, M.L.Trincavelli, C.Martini, and G.Cristalli (2009).
Adenosine A2A receptor antagonists: new 8-substituted 9-ethyladenines as tools for in vivo rat models of Parkinson's disease.

ChemMedChem, 4, 1010-1019.

19645726 S.F.Marino (2009).
High-level production and characterization of a G-protein coupled receptor signaling complex.

FEBS J, 276, 4515-4528.

19458709 S.H.White (2009).
Biophysical dissection of membrane proteins.

Nature, 459, 344-346.

19262747 S.N.Fatakia, S.Costanzi, and C.C.Chow (2009).
Computing highly correlated positions using mutual information and graph theory for G protein-coupled receptors.

PLoS ONE, 4, e4681.

19592511 S.Neumann, W.Huang, S.Titus, G.Krause, G.Kleinau, A.T.Alberobello, W.Zheng, N.T.Southall, J.Inglese, C.P.Austin, F.S.Celi, O.Gavrilova, C.J.Thomas, B.M.Raaka, and M.C.Gershengorn (2009).
Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice.

Proc Natl Acad Sci U S A, 106, 12471-12476.

19433801 T.E.Angel, M.R.Chance, and K.Palczewski (2009).
Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors.

Proc Natl Acad Sci U S A, 106, 8555-8560.

19536805 T.M.Blois, and J.U.Bowie (2009).
G-protein-coupled receptor structures were not built in a day.

Protein Sci, 18, 1335-1342.

19558453 T.Suzuki, K.Namba, R.Yamagishi, H.Kaneko, T.Haga, and H.Nakata (2009).
A highly conserved tryptophan residue in the fourth transmembrane domain of the A adenosine receptor is essential for ligand binding but not receptor homodimerization.

J Neurochem, 110, 1352-1362.

19470481 X.J.Yao, G.Vélez Ruiz, M.R.Whorton, S.G.Rasmussen, B.T.DeVree, X.Deupi, R.K.Sunahara, and B.Kobilka (2009).
The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex.

Proc Natl Acad Sci U S A, 106, 9501-9506.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.