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6oba
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6oba is ON HOLD until Paper Publication Authors: Liu, X., Stobel, A., Kaindl, J., Dengler, D., ClarK, M., Mahoney, J., Korczynska, M., Matt, R.A., H...) |
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The beta2 adrenergic receptor bound to a negative allosteric modulator== |
| + | <StructureSection load='6oba' size='340' side='right'caption='[[6oba]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6oba]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] 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=6OBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OBA 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]] 3.1Å</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=JTZ:(2S)-1-[(1-METHYLETHYL)AMINO]-3-(2-PROP-2-EN-1-YLPHENOXY)PROPAN-2-OL'>JTZ</scene>, <scene name='pdbligand=M3J:6-bromanyl-~{N}2-phenyl-quinazoline-2,4-diamine'>M3J</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=6oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oba OCA], [https://pdbe.org/6oba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oba RCSB], [https://www.ebi.ac.uk/pdbsum/6oba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oba ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/ADRB2_HUMAN ADRB2_HUMAN] Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Most drugs acting on G-protein-coupled receptors target the orthosteric binding pocket where the native hormone or neurotransmitter binds. There is much interest in finding allosteric ligands for these targets because they modulate physiologic signaling and promise to be more selective than orthosteric ligands. Here we describe a newly developed allosteric modulator of the beta2-adrenergic receptor (beta2AR), AS408, that binds to the membrane-facing surface of transmembrane segments 3 and 5, as revealed by X-ray crystallography. AS408 disrupts a water-mediated polar network involving E122(3.41) and the backbone carbonyls of V206(5.45) and S207(5.46). The AS408 binding site is adjacent to a previously identified molecular switch for beta2AR activation formed by I(3.40), P(5.50) and F(6.44). The structure reveals how AS408 stabilizes the inactive conformation of this switch, thereby acting as a negative allosteric modulator for agonists and positive allosteric modulator for inverse agonists. | ||
| - | + | An allosteric modulator binds to a conformational hub in the beta2 adrenergic receptor.,Liu X, Kaindl J, Korczynska M, Stossel A, Dengler D, Stanek M, Hubner H, Clark MJ, Mahoney J, Matt RA, Xu X, Hirata K, Shoichet BK, Sunahara RK, Kobilka BK, Gmeiner P Nat Chem Biol. 2020 Jun 1. pii: 10.1038/s41589-020-0549-2. doi:, 10.1038/s41589-020-0549-2. PMID:32483378<ref>PMID:32483378</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6oba" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]] |
| - | [[Category: Gmeiner | + | *[[Lysozyme 3D structures|Lysozyme 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Escherichia virus T4]] |
| - | [[Category: Mahoney | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: ClarK M]] |
| - | [[Category: | + | [[Category: Dengler D]] |
| - | [[Category: Sunahara | + | [[Category: Gmeiner R]] |
| - | [[Category: | + | [[Category: Hirata K]] |
| + | [[Category: Hubner H]] | ||
| + | [[Category: Kaindl J]] | ||
| + | [[Category: Kobilka BK]] | ||
| + | [[Category: Korczynska M]] | ||
| + | [[Category: Liu X]] | ||
| + | [[Category: Mahoney J]] | ||
| + | [[Category: Matt RA]] | ||
| + | [[Category: Shoichet B]] | ||
| + | [[Category: Stanek M]] | ||
| + | [[Category: Stobel A]] | ||
| + | [[Category: Sunahara R]] | ||
| + | [[Category: Xu X]] | ||
Current revision
The beta2 adrenergic receptor bound to a negative allosteric modulator
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Categories: Escherichia virus T4 | Homo sapiens | Large Structures | ClarK M | Dengler D | Gmeiner R | Hirata K | Hubner H | Kaindl J | Kobilka BK | Korczynska M | Liu X | Mahoney J | Matt RA | Shoichet B | Stanek M | Stobel A | Sunahara R | Xu X
