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5xpr

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Human endothelin receptor type-B in complex with antagonist bosentan

Structural highlights

5xpr is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	EDNRB, ETRB (HUMAN)
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.^[1]

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.^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Issa S, Bondurand N, Faubert E, Poisson S, Lecerf L, Nitschke P, Deggouj N, Loundon N, Jonard L, David A, Sznajer Y, Blanchet P, Marlin S, Pingault V. EDNRB mutations cause Waardenburg syndrome type II in the heterozygous state. Hum Mutat. 2017 May;38(5):581-593. doi: 10.1002/humu.23206. Epub 2017 Mar 15. PMID:28236341 doi:http://dx.doi.org/10.1002/humu.23206
↑ Webb ML, Chao CC, Rizzo M, Shapiro RA, Neubauer M, Liu EC, Aversa CR, Brittain RJ, Treiger B. Cloning and expression of an endothelin receptor subtype B from human prostate that mediates contraction. Mol Pharmacol. 1995 Apr;47(4):730-7. PMID:7536888
↑ Shihoya W, Nishizawa T, Yamashita K, Inoue A, Hirata K, Kadji FMN, Okuta A, Tani K, Aoki J, Fujiyoshi Y, Doi T, Nureki O. X-ray structures of endothelin ETB receptor bound to clinical antagonist bosentan and its analog. Nat Struct Mol Biol. 2017 Sep;24(9):758-764. doi: 10.1038/nsmb.3450. Epub 2017, Aug 14. PMID:28805809 doi:http://dx.doi.org/10.1038/nsmb.3450

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xpr"

@@ Line 1: / Line 1: @@
-==Crystal Structure of a Receptor_1==
+==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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XPR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xpr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XPR FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EDNRB, ETRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xpr OCA], [http://pdbe.org/5xpr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xpr RCSB], [http://www.ebi.ac.uk/pdbsum/5xpr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xpr ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Lysozyme]]
 [[Category: Doi, T]]

5xpr

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Current revision

Human endothelin receptor type-B in complex with antagonist bosentan

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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