View source for 6n48


==Structure of beta2 adrenergic receptor bound to BI167107, Nanobody 6B9, and a positive allosteric modulator==
<StructureSection load='6n48' size='340' side='right'caption='[[6n48]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6n48]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelidae Camelidae], [https://en.wikipedia.org/wiki/Enterobacteria_phage_RB59 Enterobacteria phage RB59] 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=6N48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N48 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1WV:(2S)-2,3-DIHYDROXYPROPYL+(7Z)-TETRADEC-7-ENOATE'>1WV</scene>, <scene name='pdbligand=KBY:N-[(3R)-4-(4-tert-butylphenyl)-3-({2-[(4-methoxyphenyl)sulfanyl]-5-[methyl(propan-2-yl)sulfamoyl]benzene-1-carbonyl}amino)butanoyl]glycine'>KBY</scene>, <scene name='pdbligand=P0G:8-[(1R)-2-{[1,1-DIMETHYL-2-(2-METHYLPHENYL)ETHYL]AMINO}-1-HYDROXYETHYL]-5-HYDROXY-2H-1,4-BENZOXAZIN-3(4H)-ONE'>P0G</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=6n48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n48 OCA], [https://pdbe.org/6n48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n48 RCSB], [https://www.ebi.ac.uk/pdbsum/6n48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n48 ProSAT]</span></td></tr>
</table>
== Function ==
[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 ==
Drugs targeting the orthosteric, primary binding site of G protein-coupled receptors are the most common therapeutics. Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically. We report the crystal structure of the prototypic beta2-adrenergic receptor in complex with an orthosteric agonist and compound-6FA, a positive allosteric modulator of this receptor. It binds on the receptor's inner surface in a pocket created by intracellular loop 2 and transmembrane segments 3 and 4, stabilizing the loop in an alpha-helical conformation required to engage the G protein. Structural comparison explains the selectivity of the compound for beta2- over the beta1-adrenergic receptor. Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor drugs.

Mechanism of beta2AR regulation by an intracellular positive allosteric modulator.,Liu X, Masoudi A, Kahsai AW, Huang LY, Pani B, Staus DP, Shim PJ, Hirata K, Simhal RK, Schwalb AM, Rambarat PK, Ahn S, Lefkowitz RJ, Kobilka B Science. 2019 Jun 28;364(6447):1283-1287. doi: 10.1126/science.aaw8981. Epub 2019, Jun 27. PMID:31249059<ref>PMID:31249059</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6n48" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]]
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Camelidae]]
[[Category: Enterobacteria phage RB59]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ahn S]]
[[Category: Hirata K]]
[[Category: Huang LY]]
[[Category: Kahsai AW]]
[[Category: Kobilka BK]]
[[Category: Lefkowitz RJ]]
[[Category: Liu X]]
[[Category: Masoudi A]]
[[Category: Pani B]]