9rkh

Dark structure of beta-2 Adrenergic receptor with photoazolol in Dark state recorded at LCLS

spinqualitylabelsall models 9rkh, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9rkh 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 2.5Å Ligands: 12P, A1JHU, CLR, EDO, GOL, OLC, PLM, SO4, YCM 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.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. Publication Abstract from PubMed The field of photopharmacology develops light-responsive drugs that can modulate protein activity, enabling precise and dynamic investigations of their roles in health and disease. Adrenergic receptors are prominent targets for this approach because they are prototypical G protein-coupled receptors with high clinical relevance in bronchial and cardiovascular diseases. Here, we employed the azobenzene-based compound photoazolol-1 in combination with time-resolved serial crystallography at X-ray free-electron lasers to resolve the molecular mechanisms by which photoswitchable beta-blockers modulate activity of the beta(2)-adrenoceptor (beta(2)AR). Time-resolved structures of the receptor bound to trans-photoazolol-1 (pre-photoconversion), a strained intermediate in the nanosecond range, and the fully photoisomerized cis-photoazolol-1 reveal how isomerization of the azobenzene moiety induces distinct conformational changes within the orthosteric ligand binding pocket. Within seconds, light-excited photoazolol-1 adopts a new binding pose, altering interactions with extracellular loop 2 and shifting the positions of transmembrane helices 5, 6, and 7. Functional assays of beta(2)AR in cellular membranes show that photoazolol-1 acts as an efficacy photoswitch, changing from an inverse agonist to a neutral antagonist upon isomerization without leaving the binding pocket. In combination, these findings suggest a molecular mechanism for activity modulation via efficacy photoswitches and provide a framework for designing ligands that exploit light-driven transitions within the binding pocket to achieve spatiotemporal control of receptor function. Structural Mechanism of an Efficacy Photoswitch Targeting the beta(2)-adrenergic Receptor.,Stipp R, Bertrand Q, Trabuco M, Duran-Corbera A, Ignazzitto MT, Glover H, Stierli F, Catena J, Carrillo M, Hartmann S, Seidel HP, Mulder M, Mason T, Kondo Y, Wranik M, Appleby M, Sager C, Sierra R, Gate G, Schleissner P, Cheng X, Weinert T, Cheng R, Mous S, Beale JH, Kepa M, Llebaria A, Hennig M, Rovira X, Standfuss J Angew Chem Int Ed Engl. 2026 Mar 18:e17995. doi: 10.1002/anie.202517995. PMID:41848496 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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