7b6w

<table><tr><td colspan='2'>[[7b6w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B6W FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T0B:[(4~{a}~{R},8~{a}~{S})-4-(4-azanyl-6,7-dimethoxy-quinazolin-2-yl)-2,3,4~{a},5,6,7,8,8~{a}-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone'>T0B</scene></td></tr>

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== Publication Abstract from PubMed ==

alpha-adrenergic receptors (alphaARs) are G protein-coupled receptors that regulate vital functions of the cardiovascular and nervous systems. The therapeutic potential of alphaARs, however, is largely unexploited and hampered by the scarcity of subtype-selective ligands. Moreover, several aminergic drugs either show off-target binding to alphaARs or fail to interact with the desired subtype. Here, we report the crystal structure of human alpha1BAR bound to the inverse agonist (+)-cyclazosin, enabled by the fusion to a DARPin crystallization chaperone. The alpha1BAR structure allows the identification of two unique secondary binding pockets. By structural comparison of alpha1BAR with alpha2ARs, and by constructing alpha1BAR-alpha2CAR chimeras, we identify residues 3.29 and 6.55 as key determinants of ligand selectivity. Our findings provide a basis for discovery of alpha1BAR-selective ligands and may guide the optimization of aminergic drugs to prevent off-target binding to alphaARs, or to elicit a selective interaction with the desired subtype.

 

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== References ==

[[Category: Deluigi, M]]

[[Category: Hilge, M]]

[[Category: Klipp, A]]

[[Category: Merklinger, L]]

[[Category: Morstein, L]]

[[Category: Plueckthun, A]]

[[Category: Schuster, M]]

[[Category: Scott, D J]]

[[Category: Membrane protein]]