6h7o
From Proteopedia
ACTIVATED TURKEY BETA1 ADRENOCEPTOR WITH BOUND WEAK PARTIAL AGONIST CYANOPINDOLOL AND NANOBODY Nb6B9
Structural highlights
Function[THIO_ECOLI] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. [ADRB1_MELGA] Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Publication Abstract from PubMedG protein-coupled receptors (GPCRs) in the G protein-coupled active state have higher affinity for agonists compared to when they are in the inactive state, but the molecular basis for this is unclear. We have determined four active-state structures of the beta1-adrenoceptor (beta1AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. Comparison with inactive-state structures of beta1AR bound to the identical ligands showed a 24-42% reduction in the volume of the orthosteric binding site. Potential hydrogen bonds were also shorter, and there was up to a 30% increase in the number of atomic contacts between the receptor and ligand. This explains the increase in agonist affinity of GPCRs in the active state for a wide range of structurally distinct agonists. Molecular basis for high-affinity agonist binding in GPCRs.,Warne T, Edwards PC, Dore AS, Leslie AGW, Tate CG Science. 2019 May 9. pii: science.aau5595. doi: 10.1126/science.aau5595. PMID:31072904[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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