6ps0

XFEL beta2 AR structure by ligand exchange from Alprenolol to Carazolol.

spinqualitylabelsall models 6ps0, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ps0 is a 1 chain structure with sequence from Escherichia virus T4 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 3.4Å Ligands: CAU, CLR, OLA, OLC, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D9IEF7_BPT4 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adrenergic receptor 3D structures Lysozyme 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA