View source for 5uen


==Crystal structure of the human adenosine A1 receptor A1AR-bRIL in complex with the covalent antagonist DU172 at 3.2A resolution==
<StructureSection load='5uen' size='340' side='right'caption='[[5uen]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5uen]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UEN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DU1:4-{[3-(8-CYCLOHEXYL-2,6-DIOXO-1-PROPYL-1,2,6,7-TETRAHYDRO-3H-PURIN-3-YL)PROPYL]CARBAMOYL}BENZENE-1-SULFONYL+FLUORIDE'>DU1</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5uen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uen OCA], [https://pdbe.org/5uen PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uen RCSB], [https://www.ebi.ac.uk/pdbsum/5uen PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uen ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/AA1R_HUMAN AA1R_HUMAN] Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The adenosine A1 receptor (A1-AR) is a G-protein-coupled receptor that plays a vital role in cardiac, renal, and neuronal processes but remains poorly targeted by current drugs. We determined a 3.2 A crystal structure of the A1-AR bound to the selective covalent antagonist, DU172, and identified striking differences to the previously solved adenosine A2A receptor (A2A-AR) structure. Mutational and computational analysis of A1-AR revealed a distinct conformation of the second extracellular loop and a wider extracellular cavity with a secondary binding pocket that can accommodate orthosteric and allosteric ligands. We propose that conformational differences in these regions, rather than amino-acid divergence, underlie drug selectivity between these adenosine receptor subtypes. Our findings provide a molecular basis for AR subtype selectivity with implications for understanding the mechanisms governing allosteric modulation of these receptors, allowing the design of more selective agents for the treatment of ischemia-reperfusion injury, renal pathologies, and neuropathic pain.

Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity.,Glukhova A, Thal DM, Nguyen AT, Vecchio EA, Jorg M, Scammells PJ, May LT, Sexton PM, Christopoulos A Cell. 2017 Feb 23;168(5):867-877.e13. doi: 10.1016/j.cell.2017.01.042. PMID:28235198<ref>PMID:28235198</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5uen" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Christopoulos A]]
[[Category: Glukhova A]]
[[Category: Jorg M]]
[[Category: May LT]]
[[Category: Nguyen AT]]
[[Category: Scammells PJ]]
[[Category: Sexton PM]]
[[Category: Thal DM]]
[[Category: Vecchio EA]]