7br3 | pdb_00007br3

Crystal structure of the protein 1

spinqualitylabelsall models 7br3, resolution 2.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7br3 is a 1 chain structure with sequence from Homo sapiens and Pyrococcus abyssi GE5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.79Å Ligands: 1QW, F5O, FMT, OLC, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GNRHR_HUMAN Normosmic congenital hypogonadotropic hypogonadism. The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in GNRHR as well as in other HH-associated genes including FGFR1 (PubMed:23643382). Function GNRHR_HUMAN Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.Q9V2J8_PYRAB Publication Abstract from PubMed Gonadotrophin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone, is the main regulator of the reproductive system, acting on gonadotropic cells by binding to the GnRH1 receptor (GnRH1R). The GnRH-GnRH1R system is a promising therapeutic target for maintaining reproductive function; to date, a number of ligands targeting GnRH1R for disease treatment are available on the market. Here, we report the crystal structure of GnRH1R bound to the small-molecule drug elagolix at 2.8 A resolution. The structure reveals an interesting N-terminus that could co-occupy the enlarged orthosteric binding site together with elagolix. The unusual ligand binding mode was further investigated by structural analyses, functional assays and molecular docking studies. On the other hand, because of the unique characteristic of lacking a cytoplasmic C-terminal helix, GnRH1R exhibits different microswitch structural features from other class A GPCRs. In summary, this study provides insight into the ligand binding mode of GnRH1R and offers an atomic framework for rational drug design. Structure of the human gonadotropin-releasing hormone receptor GnRH1R reveals an unusual ligand binding mode.,Yan W, Cheng L, Wang W, Wu C, Yang X, Du X, Ma L, Qi S, Wei Y, Lu Z, Yang S, Shao Z Nat Commun. 2020 Oct 20;11(1):5287. doi: 10.1038/s41467-020-19109-w. PMID:33082324 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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