3ny9: Difference between revisions

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-[[Image:3ny9.png|left|200px]]
-{{STRUCTURE_3ny9|  PDB=3ny9  |  SCENE=  }}
+==Crystal structure of the human beta2 adrenergic receptor in complex with a novel inverse agonist==
+<StructureSection load='3ny9' size='340' side='right'caption='[[3ny9]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3ny9]] 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=3NY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NY9 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]] 2.84&#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=JSZ:ETHYL+4-({(2S)-2-HYDROXY-3-[(1-METHYLETHYL)AMINO]PROPYL}OXY)-3-METHYL-1-BENZOFURAN-2-CARBOXYLATE'>JSZ</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</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=3ny9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ny9 OCA], [https://pdbe.org/3ny9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ny9 RCSB], [https://www.ebi.ac.uk/pdbsum/3ny9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ny9 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ny/3ny9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ny9 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+G protein-coupled receptors (GPCRs) represent a large fraction of current pharmaceutical targets, and of the GPCRs, the beta(2) adrenergic receptor (beta(2)AR) is one of the most extensively studied. Previously, the X-ray crystal structure of beta(2)AR has been determined in complex with two partial inverse agonists, but the global impact of additional ligands on the structure or local impacts on the binding site are not well-understood. To assess the extent of such ligand-induced conformational differences, we determined the crystal structures of a previously described engineered beta(2)AR construct in complex with two inverse agonists: ICI 118,551 (2.8 A), a recently described compound (2.8 A) (Kolb et al, 2009), and the antagonist alprenolol (3.1 A). The structures show the same overall fold observed for the previous beta(2)AR structures and demonstrate that the ligand binding site can accommodate compounds of different chemical and pharmacological properties with only minor local structural rearrangements. All three compounds contain a hydroxy-amine motif that establishes a conserved hydrogen bond network with the receptor and chemically diverse aromatic moieties that form distinct interactions with beta(2)AR. Furthermore, receptor ligand cross-docking experiments revealed that a single beta(2)AR complex can be suitable for docking of a range of antagonists and inverse agonists but also indicate that additional ligand-receptor structures may be useful to further improve performance for in-silico docking or lead-optimization in drug design.
-===Crystal structure of the human beta2 adrenergic receptor in complex with a novel inverse agonist===
+Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography.,Wacker D, Fenalti G, Brown MA, Katritch V, Abagyan R, Cherezov V, Stevens RC J Am Chem Soc. 2010 Aug 25;132(33):11443-5. PMID:20669948<ref>PMID:20669948</ref>
-{{ABSTRACT_PUBMED_20669948}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3ny9" style="background-color:#fffaf0;"></div>
-[[3ny9]] is a 1 chain structure of [[Adrenergic receptor]] and [[Hen Egg-White (HEW) Lysozyme]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens,_enterobacteria_phage_t4 Homo sapiens, enterobacteria phage t4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NY9 OCA].
 ==See Also==
-*[[Adrenergic receptor|Adrenergic receptor]]
+*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]]
-*[[Hen Egg-White (HEW) Lysozyme|Hen Egg-White (HEW) Lysozyme]]
+*[[Lysozyme 3D structures|Lysozyme 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020669948</ref><references group="xtra"/>
+__TOC__
-[[Category: Homo sapiens, enterobacteria phage t4]]
+</StructureSection>
-[[Category: ATCG3D, Accelerated Technologies Center for Gene to 3D Structure.]]
+[[Category: Escherichia virus T4]]
-[[Category: Abagyan, R.]]
+[[Category: Homo sapiens]]
-[[Category: Brown, M A.]]
+[[Category: Large Structures]]
-[[Category: Cherezov, V.]]
+[[Category: Abagyan R]]
-[[Category: Fenalti, G.]]
+[[Category: Brown MA]]
-[[Category: GPCR, GPCR Network.]]
+[[Category: Cherezov V]]
-[[Category: Katritch, V.]]
+[[Category: Fenalti G]]
-[[Category: Stevens, R C.]]
+[[Category: Katritch V]]
-[[Category: Wacker, D.]]
+[[Category: Stevens RC]]
-[[Category: Accelerated technologies center for gene to 3d structure]]
+[[Category: Wacker D]]
-[[Category: Adrenalin]]
-[[Category: Adrenergic]]
-[[Category: Arrestin]]
-[[Category: Atcg3d]]
-[[Category: Compound 2]]
-[[Category: Fusion]]
-[[Category: G protein-coupled receptor]]
-[[Category: G-protein]]
-[[Category: Glycosylation]]
-[[Category: Hydrolase]]
-[[Category: Lysozyme]]
-[[Category: Membrane protein]]
-[[Category: Palmitoylation]]
-[[Category: Phosphorylation]]
-[[Category: Protein structure initiative]]
-[[Category: Psi-2]]
-[[Category: Structural genomic]]
-[[Category: Transducer]]