5N2S

Crystal structure of stabilized A1 receptor in complex with PSB36 at 3.3A resolution

Summary for 5N2S

• Entry DOI: 10.2210/pdb5n2s/pdb
• Descriptor: Soluble cytochrome b562,Adenosine receptor A1, 1-butyl-3-(3-oxidanylpropyl)-8-[(1~{R},5~{S})-3-tricyclo[3.3.1.0^{3,7}]nonanyl]-7~{H}-purine-2,6-dione, SULFATE ION, ... (4 entities in total)
• Functional Keywords: g-protein-coupled receptor, integral thermostabilizing mutations, membrane protein
• Biological source: Escherichia coli; More
• Cellular location: Cell membrane ; Multi-pass membrane protein: P30542
• Total number of polymer chains: 1
• Total formula weight: 49024.47

Authors

Cheng, R.K.Y.,Segala, E.,Robertson, N.,Deflorian, F.,Dore, A.S.,Errey, J.C.,Fiez-Vandal, C.,Marshall, F.H.,Cooke, R.M. (deposition date: 2017-02-08, release date: 2017-07-26, Last modification date: 2024-11-13)

Primary citation

Cheng, R.K.Y.,Segala, E.,Robertson, N.,Deflorian, F.,Dore, A.S.,Errey, J.C.,Fiez-Vandal, C.,Marshall, F.H.,Cooke, R.M.
Structures of Human A1 and A2A Adenosine Receptors with Xanthines Reveal Determinants of Selectivity.
Structure, 25:1275-1285.e4, 2017

PubMed Abstract: The adenosine A and A receptors belong to the purinergic family of G protein-coupled receptors, and regulate diverse functions of the cardiovascular, respiratory, renal, inflammation, and CNS. Xanthines such as caffeine and theophylline are weak, non-selective antagonists of adenosine receptors. Here we report the structure of a thermostabilized human A receptor at 3.3 Å resolution with PSB36, an A-selective xanthine-based antagonist. This is compared with structures of the A receptor with PSB36 (2.8 Å resolution), caffeine (2.1 Å), and theophylline (2.0 Å) to highlight features of ligand recognition which are common across xanthines. The structures of AR and AR were analyzed to identify the differences that are important selectivity determinants for xanthine ligands, and the role of T270 in AR (M270 in AR) in conferring selectivity was confirmed by mutagenesis. The structural differences confirmed to lead to selectivity can be utilized in the design of new subtype-selective AR or AR antagonists.

PubMed: 28712806
DOI: 10.1016/j.str.2017.06.012

Experimental method

X-RAY DIFFRACTION (3.303 Å)