8ha0

Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1

spinqualitylabelsall models 8ha0, resolution 2.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ha0 is a 6 chain structure with sequence from Bos taurus, Homo sapiens, Rattus norvegicus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.62Å Ligands: CLR, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 A and 3.25 A, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders. Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.,Zhao LH, Yuan QN, Dai AT, He XH, Chen CW, Zhang C, Xu YW, Zhou Y, Wang MW, Yang DH, Xu HE Acta Pharmacol Sin. 2023 Jun;44(6):1227-1237. doi: 10.1038/s41401-022-01032-z. , Epub 2022 Dec 8. PMID:36482086 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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