6n48

Structure of beta2 adrenergic receptor bound to BI167107, Nanobody 6B9, and a positive allosteric modulator

spinqualitylabelsall models 6n48, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6n48 is a 2 chain structure with sequence from Camelidae, Enterobacteria phage RB59 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: 1WV, KBY, P0G Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adrenergic receptor 3D structures Antibody 3D structures

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