7ej8: Difference between revisions

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[7ej8]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EJ8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J59:Brimonidine'>J59</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J59:5-bromanyl-~{N}-(4,5-dihydro-1~{H}-imidazol-2-yl)quinoxalin-6-amine'>J59</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=7ej8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ej8 OCA], [https://pdbe.org/7ej8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ej8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ej8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ej8 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[https://www.uniprot.org/uniprot/GNAO_HUMAN GNAO_HUMAN] Early infantile epileptic encephalopathy. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
-== Function ==
-[https://www.uniprot.org/uniprot/GNAO_HUMAN GNAO_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-The alpha2A adrenergic receptor (alpha2AAR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo-electron microscopy structures of the human alpha2AAR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the alpha2AAR. Further structural analyses uncover different molecular determinants between alpha2AAR and betaARs for recognition of norepinephrine and key regions that determine the G protein coupling selectivity. Overall, our studies provide a framework for understanding the signal transduction of the adrenergic system at the atomic level, which will facilitate rational structure-based discovery of safer and more effective medications for alpha2AAR.
+The alpha(2A) adrenergic receptor (alpha(2A)AR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo-electron microscopy structures of the human alpha(2A)AR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the alpha(2A)AR. Further structural analyses uncover different molecular determinants between alpha(2A)AR and betaARs for recognition of norepinephrine and key regions that determine the G protein coupling selectivity. Overall, our studies provide a framework for understanding the signal transduction of the adrenergic system at the atomic level, which will facilitate rational structure-based discovery of safer and more effective medications for alpha(2A)AR.
-Structural insights into ligand recognition, activation, and signaling of the alpha2A adrenergic receptor.,Xu J, Cao S, Hubner H, Weikert D, Chen G, Lu Q, Yuan D, Gmeiner P, Liu Z, Du Y Sci Adv. 2022 Mar 4;8(9):eabj5347. doi: 10.1126/sciadv.abj5347. Epub 2022 Mar 4. PMID:35245122<ref>PMID:35245122</ref>
+Structural insights into ligand recognition, activation, and signaling of the alpha(2A) adrenergic receptor.,Xu J, Cao S, Hubner H, Weikert D, Chen G, Lu Q, Yuan D, Gmeiner P, Liu Z, Du Y Sci Adv. 2022 Mar 4;8(9):eabj5347. doi: 10.1126/sciadv.abj5347. Epub 2022 Mar 4. PMID:35245122<ref>PMID:35245122</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>