3EML

The 2.6 A Crystal Structure of a Human A2A Adenosine Receptor bound to ZM241385.

Summary for 3EML

• Entry DOI: 10.2210/pdb3eml/pdb
• Descriptor: Human Adenosine A2A receptor/T4 lysozyme chimera, 4-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenol, STEARIC ACID, ... (5 entities in total)
• Functional Keywords: adenosine, caffeine, gpcr, membrane protein, receptor, lcp, mesophase, structural genomics, psi-2, protein structure initiative, accelerated technologies center for gene to 3d structure, atcg3d, gpcr network
• Biological source: Homo sapiens; More
• Cellular location: Cell membrane; Multi-pass membrane protein: P29274
• Total number of polymer chains: 1
• Total formula weight: 57171.93

Authors

Jaakola, V.-P.,Griffith, M.T.,Hanson, M.A.,Cherezov, V.,Chien, E.Y.T.,Lane, J.R.,Ijzerman, A.P.,Stevens, R.C.,Accelerated Technologies Center for Gene to 3D Structure (ATCG3D),GPCR Network (GPCR) (deposition date: 2008-09-24, release date: 2008-10-14, Last modification date: 2024-10-30)

Primary citation

Jaakola, V.P.,Griffith, M.T.,Hanson, M.A.,Cherezov, V.,Chien, E.Y.,Lane, J.R.,Ijzerman, A.P.,Stevens, R.C.
The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist.
Science, 322:1211-1217, 2008

PubMed 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 A2A 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.

PubMed: 18832607
DOI: 10.1126/science.1164772

Experimental method

X-RAY DIFFRACTION (2.6 Å)