5uen: Difference between revisions
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The | ==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]] 3.20Å' 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]] 3.2Å</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </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]] | |||
Latest revision as of 13:26, 4 October 2023
Crystal structure of the human adenosine A1 receptor A1AR-bRIL in complex with the covalent antagonist DU172 at 3.2A resolution
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