View source for 5xpr


==Human endothelin receptor type-B in complex with antagonist bosentan==
<StructureSection load='5xpr' size='340' side='right'caption='[[5xpr]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xpr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XPR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K86:4-~{tert}-butyl-~{N}-[6-(2-hydroxyethyloxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-yl-pyrimidin-4-yl]benzenesulfonamide'>K86</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5xpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xpr OCA], [https://pdbe.org/5xpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xpr RCSB], [https://www.ebi.ac.uk/pdbsum/5xpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xpr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/EDNRB_HUMAN 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.<ref>PMID:28236341</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ENLYS_BPT4 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.<ref>PMID:22389108</ref> [https://www.uniprot.org/uniprot/EDNRB_HUMAN 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.<ref>PMID:7536888</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:28805809</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xpr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Doi T]]
[[Category: Fujiyoshi Y]]
[[Category: Hirata K]]
[[Category: Nishizawa T]]
[[Category: Nureki O]]
[[Category: Okuta A]]
[[Category: Shihoya W]]
[[Category: Tani K]]
[[Category: Yamashita K]]