5x93

From Proteopedia

(Difference between revisions)

Current revision

Human endothelin receptor type-B in complex with antagonist K-8794

Structural highlights

5x93 is a 1 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:	, , ,
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

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.^[2] 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.^[3]

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^[4]

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
↑ Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:http://dx.doi.org/10.1002/pro.2042
↑ 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/5x93"

@@ Line 1: / Line 1: @@
-==Crystal Structure of a Receptor_2==
+==Human endothelin receptor type-B in complex with antagonist K-8794==
-<StructureSection load='5x93' size='340' side='right' caption='[[5x93]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='5x93' size='340' side='right'caption='[[5x93]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5x93]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X93 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5x93]] 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=5X93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X93 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=K87:3-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-pyrimidin-2-yl-pyrimidin-4-yl]oxy-N-(2,6-dimethylphenyl)propanamide'>K87</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=K87:3-[6-[(4-~{tert}-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-pyrimidin-2-yl-pyrimidin-4-yl]oxy-~{N}-(2,6-dimethylphenyl)propanamide'>K87</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5x93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x93 OCA], [http://pdbe.org/5x93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x93 RCSB], [http://www.ebi.ac.uk/pdbsum/5x93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x93 ProSAT]</span></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=5x93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x93 OCA], [https://pdbe.org/5x93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x93 RCSB], [https://www.ebi.ac.uk/pdbsum/5x93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x93 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://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>
+[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 ==
-[[http://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>
+[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 ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Lysozyme]]
+[[Category: Escherichia virus T4]]
-[[Category: Doi, T]]
+[[Category: Homo sapiens]]
-[[Category: Fujiyoshi, Y]]
+[[Category: Large Structures]]
-[[Category: Hirata, K]]
+[[Category: Doi T]]
-[[Category: Nishizawa, T]]
+[[Category: Fujiyoshi Y]]
-[[Category: Nureki, O]]
+[[Category: Hirata K]]
-[[Category: Okuta, A]]
+[[Category: Nishizawa T]]
-[[Category: Shihoya, W]]
+[[Category: Nureki O]]
-[[Category: Tani, K]]
+[[Category: Okuta A]]
-[[Category: Yamashita, K]]
+[[Category: Shihoya W]]
-[[Category: Alpha helical]]
+[[Category: Tani K]]
-[[Category: Signaling protein]]
+[[Category: Yamashita K]]

5x93

From Proteopedia

Current revision

Human endothelin receptor type-B in complex with antagonist K-8794

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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