5uig
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of adenosine A2A receptor bound to a novel triazole-carboximidamide antagonist== | |
| + | <StructureSection load='5uig' size='340' side='right' caption='[[5uig]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5uig]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UIG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UIG FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8D1:5-AMINO-N-[(2-METHOXYPHENYL)METHYL]-2-(3-METHYLPHENYL)-2H-1,2,3-TRIAZOLE-4-CARBOXIMIDAMIDE'>8D1</scene>, <scene name='pdbligand=EDT:{[-(BIS-CARBOXYMETHYL-AMINO)-ETHYL]-CARBOXYMETHYL-AMINO}-ACETIC+ACID'>EDT</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5uig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uig OCA], [http://pdbe.org/5uig PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uig RCSB], [http://www.ebi.ac.uk/pdbsum/5uig PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uig ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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 == | ||
| + | The adenosine A2A receptor (A2AR) has long been implicated in cardiovascular disorders. As more selective A2AR ligands are being identified, its roles in other disorders, such as Parkinson's disease, are starting to emerge, and A2AR antagonists are important drug candidates for nondopaminergic anti-Parkinson treatment. Here we report the crystal structure of A2A receptor bound to compound 1 (Cmpd-1), a novel A2AR/N-methyl d-aspartate receptor subtype 2B (NR2B) dual antagonist and potential anti-Parkinson candidate compound, at 3.5 A resolution. The A2A receptor with a cytochrome b562-RIL (BRIL) fusion (A2AR-BRIL) in the intracellular loop 3 (ICL3) was crystallized in detergent micelles using vapor-phase diffusion. Whereas A2AR-BRIL bound to the antagonist ZM241385 has previously been crystallized in lipidic cubic phase (LCP), structural differences in the Cmpd-1-bound A2AR-BRIL prevented formation of the lattice observed with the ZM241385-bound receptor. The crystals grew with a type II crystal lattice in contrast to the typical type I packing seen from membrane protein structures crystallized in LCP. Cmpd-1 binds in a position that overlaps with the native ligand adenosine, but its methoxyphenyl group extends to an exosite not previously observed in other A2AR structures. Structural analysis revealed that Cmpd-1 binding results in the unique conformations of two tyrosine residues, Tyr91.35 and Tyr2717.36, which are critical for the formation of the exosite. The structure reveals insights into antagonist binding that are not observed in other A2AR structures, highlighting flexibility in the binding pocket that may facilitate the development of A2AR-selective compounds for the treatment of Parkinson's disease. | ||
| - | + | Crystal structure of the adenosine A2A receptor bound to an antagonist reveals a potential allosteric pocket.,Sun B, Bachhawat P, Chu ML, Wood M, Ceska T, Sands ZA, Mercier J, Lebon F, Kobilka TS, Kobilka BK Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):2066-2071. doi:, 10.1073/pnas.1621423114. Epub 2017 Feb 6. PMID:28167788<ref>PMID:28167788</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[ | + | </div> |
| + | <div class="pdbe-citations 5uig" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Adenosine A2A receptor|Adenosine A2A receptor]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Bachhawat, P]] | [[Category: Bachhawat, P]] | ||
[[Category: Ceska, T]] | [[Category: Ceska, T]] | ||
| - | [[Category: | + | [[Category: Chu, M Ling-Hon]] |
| - | + | ||
| - | + | ||
| - | + | ||
[[Category: Kobilka, B]] | [[Category: Kobilka, B]] | ||
| + | [[Category: Kobilka, T S]] | ||
[[Category: Lebon, F]] | [[Category: Lebon, F]] | ||
| + | [[Category: Sands, Z]] | ||
| + | [[Category: Sun, B]] | ||
| + | [[Category: A2a receptor]] | ||
| + | [[Category: Adenosine]] | ||
| + | [[Category: Adenosine binding protein]] | ||
| + | [[Category: Allosteric]] | ||
| + | [[Category: Gpcr]] | ||
| + | [[Category: Parkinson's disease]] | ||
| + | [[Category: Vapor diffusion]] | ||
Revision as of 07:14, 9 March 2017
Crystal structure of adenosine A2A receptor bound to a novel triazole-carboximidamide antagonist
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