5xpr

Crystal Structure of a Receptor_1

spinqualitylabelsall models 5xpr, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xpr is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: K86, SO4 Activity: Lysozyme, with EC number 3.2.1.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [EDNRB_HUMAN] Hirschsprung disease;Waardenburg-Shah syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Defects in EDNRB are associated with Waardenburg syndrome 2, with ocular albinism, autosomal recessive: A disorder characterized by the association of features typical of Waardenburg syndrome type 2 with ocular albinism. Patients manifest reduced visual acuity, albinotic fundus, deafness, hypomelanosis. Function [EDNRB_HUMAN] Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Publication Abstract from PubMed Endothelin receptors (ETRs) have crucial roles in vascular control and are targets for drugs designed to treat circulatory-system diseases and cancer progression. The nonpeptide dual-ETR antagonist bosentan is the first oral drug approved to treat pulmonary arterial hypertension. Here we report crystal structures of human endothelin ETB receptor bound to bosentan and to the ETB-selective analog K-8794, at 3.6-A and 2.2-A resolution, respectively. The K-8794-bound structure reveals the detailed water-mediated hydrogen-bonding network at the transmembrane core, which could account for the weak negative allosteric modulation of ETB by Na+ ions. The bosentan-bound structure reveals detailed interactions with ETB, which are probably conserved in the ETA receptor. A comparison of the two structures shows unexpected similarity between antagonist and agonist binding. Despite this similarity, bosentan sterically prevents the inward movement of transmembrane helix 6 (TM6), and thus exerts its antagonistic activity. These structural insights will facilitate the rational design of new ETR-targeting drugs. X-ray structures of endothelin ETB receptor bound to clinical antagonist bosentan and its analog.,Shihoya W, Nishizawa T, Yamashita K, Inoue A, Hirata K, Kadji FMN, Okuta A, Tani K, Aoki J, Fujiyoshi Y, Doi T, Nureki O Nat Struct Mol Biol. 2017 Sep;24(9):758-764. doi: 10.1038/nsmb.3450. Epub 2017, Aug 14. PMID:28805809 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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