View source for 6ps0


==XFEL beta2 AR structure by ligand exchange from Alprenolol to Carazolol.==
<StructureSection load='6ps0' size='340' side='right'caption='[[6ps0]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ps0]] 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=6PS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PS0 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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAU:(2S)-1-(9H-CARBAZOL-4-YLOXY)-3-(ISOPROPYLAMINO)PROPAN-2-OL'>CAU</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6ps0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ps0 OCA], [https://pdbe.org/6ps0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ps0 RCSB], [https://www.ebi.ac.uk/pdbsum/6ps0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ps0 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 ==
Rational structure-based drug design (SBDD) relies on the availability of a large number of co-crystal structures to map the ligand-binding pocket of the target protein and use this information for lead-compound optimization via an iterative process. While SBDD has proven successful for many drug-discovery projects, its application to G protein-coupled receptors (GPCRs) has been limited owing to extreme difficulties with their crystallization. Here, a method is presented for the rapid determination of multiple co-crystal structures for a target GPCR in complex with various ligands, taking advantage of the serial femtosecond crystallography approach, which obviates the need for large crystals and requires only submilligram quantities of purified protein. The method was applied to the human beta2-adrenergic receptor, resulting in eight room-temperature co-crystal structures with six different ligands, including previously unreported structures with carvedilol and propranolol. The generality of the proposed method was tested with three other receptors. This approach has the potential to enable SBDD for GPCRs and other difficult-to-crystallize membrane proteins.

Toward G protein-coupled receptor structure-based drug design using X-ray lasers.,Ishchenko A, Stauch B, Han GW, Batyuk A, Shiriaeva A, Li C, Zatsepin N, Weierstall U, Liu W, Nango E, Nakane T, Tanaka R, Tono K, Joti Y, Iwata S, Moraes I, Gati C, Cherezov V IUCrJ. 2019 Oct 24;6(Pt 6):1106-1119. doi: 10.1107/S2052252519013137. eCollection, 2019 Nov 1. PMID:31709066<ref>PMID:31709066</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ps0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]]
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Batyuk A]]
[[Category: Cherezov C]]
[[Category: Gati C]]
[[Category: Han GW]]
[[Category: Ishchenko A]]
[[Category: Iwata S]]
[[Category: Joti Y]]
[[Category: Li C]]
[[Category: Liu W]]
[[Category: Moraes I]]
[[Category: Nakane T]]
[[Category: Nango E]]
[[Category: Shiriaeva A]]
[[Category: Stauch B]]
[[Category: Tanaka R]]
[[Category: Tono K]]
[[Category: Weierstall U]]
[[Category: Zatsepin NA]]