View source for 3pds


==Irreversible Agonist-Beta2 Adrenoceptor Complex==
<StructureSection load='3pds' size='340' side='right'caption='[[3pds]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pds]] 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=3PDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PDS 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]] 3.5&#8491;</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=ERC:8-HYDROXY-5-[(1R)-1-HYDROXY-2-({2-[3-METHOXY-4-(3-SULFANYLPROPOXY)PHENYL]ETHYL}AMINO)ETHYL]QUINOLIN-2(1H)-ONE'>ERC</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=3pds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pds OCA], [https://pdbe.org/3pds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pds RCSB], [https://www.ebi.ac.uk/pdbsum/3pds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pds 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.[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
G-protein-coupled receptors (GPCRs) are eukaryotic integral membrane proteins that modulate biological function by initiating cellular signalling in response to chemically diverse agonists. Despite recent progress in the structural biology of GPCRs, the molecular basis for agonist binding and allosteric modulation of these proteins is poorly understood. Structural knowledge of agonist-bound states is essential for deciphering the mechanism of receptor activation, and for structure-guided design and optimization of ligands. However, the crystallization of agonist-bound GPCRs has been hampered by modest affinities and rapid off-rates of available agonists. Using the inactive structure of the human beta(2) adrenergic receptor (beta(2)AR) as a guide, we designed a beta(2)AR agonist that can be covalently tethered to a specific site on the receptor through a disulphide bond. The covalent beta(2)AR-agonist complex forms efficiently, and is capable of activating a heterotrimeric G protein. We crystallized a covalent agonist-bound beta(2)AR-T4L fusion protein in lipid bilayers through the use of the lipidic mesophase method, and determined its structure at 3.5 A resolution. A comparison to the inactive structure and an antibody-stabilized active structure (companion paper) shows how binding events at both the extracellular and intracellular surfaces are required to stabilize an active conformation of the receptor. The structures are in agreement with long-timescale (up to 30 mus) molecular dynamics simulations showing that an agonist-bound active conformation spontaneously relaxes to an inactive-like conformation in the absence of a G protein or stabilizing antibody.

Structure and function of an irreversible agonist-beta(2) adrenoceptor complex.,Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, Rasmussen SG, Choi HJ, Devree BT, Sunahara RK, Chae PS, Gellman SH, Dror RO, Shaw DE, Weis WI, Caffrey M, Gmeiner P, Kobilka BK Nature. 2011 Jan 13;469(7329):236-40. PMID:21228876<ref>PMID:21228876</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pds" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]]
*[[Beta-2 adrenergic receptor|Beta-2 adrenergic receptor]]
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aragao D]]
[[Category: Arlow DH]]
[[Category: Caffrey M]]
[[Category: Chae PS]]
[[Category: Choi H-J]]
[[Category: DeVree BT]]
[[Category: Dror RO]]
[[Category: Gellman SH]]
[[Category: Gmeiner P]]
[[Category: Holl R]]
[[Category: Kobilka BK]]
[[Category: Lyons JA]]
[[Category: Rasmussen SGF]]
[[Category: Rosenbaum DM]]
[[Category: Shaw DE]]
[[Category: Sunahara RK]]
[[Category: Weis WI]]
[[Category: Zhang C]]