7aro: Difference between revisions
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==Crystal structure of the non-ribose partial agonist LUF5833 bound to the adenosine A2A receptor== | ==Crystal structure of the non-ribose partial agonist LUF5833 bound to the adenosine A2A receptor== | ||
<StructureSection load='7aro' size='340' side='right'caption='[[7aro]]' scene=''> | <StructureSection load='7aro' size='340' side='right'caption='[[7aro]], [[Resolution|resolution]] 3.12Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ARO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARO FirstGlance]. <br> | <table><tr><td colspan='2'>[[7aro]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ARO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARO FirstGlance]. <br> | ||
</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=7aro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aro OCA], [https://pdbe.org/7aro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aro RCSB], [https://www.ebi.ac.uk/pdbsum/7aro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aro ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=RVZ:2-azanyl-6-(1~{H}-imidazol-2-ylmethylsulfanyl)-4-phenyl-pyridine-3,5-dicarbonitrile'>RVZ</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADORA2A, ADORA2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=7aro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aro OCA], [https://pdbe.org/7aro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aro RCSB], [https://www.ebi.ac.uk/pdbsum/7aro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aro ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/AA2AR_HUMAN AA2AR_HUMAN]] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In this study, we determined the crystal structure of an engineered human adenosine A2A receptor bound to a partial agonist and compared it to structures cocrystallized with either a full agonist or an antagonist/inverse agonist. The interaction between the partial agonist, belonging to a class of dicyanopyridines, and amino acids in the ligand binding pocket inspired us to develop a small library of derivatives and assess their affinity in radioligand binding studies and potency and intrinsic activity in a functional, label-free, intact cell assay. It appeared that some of the derivatives retained the partial agonist profile, whereas other ligands turned into inverse agonists. We rationalized this remarkable behavior with additional computational docking studies. | |||
Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A2A Receptor.,Amelia T, van Veldhoven JPD, Falsini M, Liu R, Heitman LH, van Westen GJP, Segala E, Verdon G, Cheng RKY, Cooke RM, van der Es D, IJzerman AP J Med Chem. 2021 Mar 25. doi: 10.1021/acs.jmedchem.0c01856. PMID:33764785<ref>PMID:33764785</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7aro" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus coli migula 1895]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Amelia T]] | [[Category: Amelia, T]] | ||
[[Category: Cheng R]] | [[Category: Cheng, R]] | ||
[[Category: Cooke R]] | [[Category: Cooke, R]] | ||
[[Category: Falsini M]] | [[Category: Es, D van der]] | ||
[[Category: Heitman L]] | [[Category: Falsini, M]] | ||
[[Category: Ijzerman A]] | [[Category: Heitman, L]] | ||
[[Category: Liu R]] | [[Category: Ijzerman, A]] | ||
[[Category: Segala E]] | [[Category: Liu, R]] | ||
[[Category: Verdon G]] | [[Category: Segala, E]] | ||
[[Category: | [[Category: Veldhoven, J van]] | ||
[[Category: | [[Category: Verdon, G]] | ||
[[Category: | [[Category: Westen, G van]] | ||
[[Category: G protein-coupled receptor]] | |||
[[Category: Gpcr]] | |||
[[Category: Membrane protein]] | |||
[[Category: Partial agonist]] | |||
[[Category: Receptor]] | |||