6rz9

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the human cysteinyl leukotriene receptor 2 in complex with ONO-2770372

Structural highlights

6rz9 is a 1 chain structure with sequence from Escherichia coli 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 2.73Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CLTR2_HUMAN Uveal melanoma.

Function

C562_ECOLX Electron-transport protein of unknown function.CLTR2_HUMAN Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4.

Publication Abstract from PubMed

Cysteinyl leukotriene G protein-coupled receptors CysLT1 and CysLT2 regulate pro-inflammatory responses associated with allergic disorders. While selective inhibition of CysLT1R has been used for treating asthma and associated diseases for over two decades, CysLT2R has recently started to emerge as a potential drug target against atopic asthma, brain injury and central nervous system disorders, as well as several types of cancer. Here, we describe four crystal structures of CysLT2R in complex with three dual CysLT1R/CysLT2R antagonists. The reported structures together with the results of comprehensive mutagenesis and computer modeling studies shed light on molecular determinants of CysLTR ligand selectivity and specific effects of disease-related single nucleotide variants.

Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.,Gusach A, Luginina A, Marin E, Brouillette RL, Besserer-Offroy E, Longpre JM, Ishchenko A, Popov P, Patel N, Fujimoto T, Maruyama T, Stauch B, Ergasheva M, Romanovskaia D, Stepko A, Kovalev K, Shevtsov M, Gordeliy V, Han GW, Katritch V, Borshchevskiy V, Sarret P, Mishin A, Cherezov V Nat Commun. 2019 Dec 6;10(1):5573. doi: 10.1038/s41467-019-13348-2. PMID:31811124^[1]

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

References

↑ Gusach A, Luginina A, Marin E, Brouillette RL, Besserer-Offroy E, Longpre JM, Ishchenko A, Popov P, Patel N, Fujimoto T, Maruyama T, Stauch B, Ergasheva M, Romanovskaia D, Stepko A, Kovalev K, Shevtsov M, Gordeliy V, Han GW, Katritch V, Borshchevskiy V, Sarret P, Mishin A, Cherezov V. Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors. Nat Commun. 2019 Dec 6;10(1):5573. doi: 10.1038/s41467-019-13348-2. PMID:31811124 doi:http://dx.doi.org/10.1038/s41467-019-13348-2

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/6rz9"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[6rz9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=6RZ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RZ9 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]] 2.73&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=KO5:(2~{S})-8-[[4-[4-(5-fluoranyl-2-methyl-phenyl)butoxy]phenyl]carbonylamino]-4-(4-oxidanyl-4-oxidanylidene-butyl)-2,3-dih+ydro-1,4-benzoxazine-2-carboxylic+acid'>KO5</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=KO5:(2~{S})-8-[[4-[4-(5-fluoranyl-2-methyl-phenyl)butoxy]phenyl]carbonylamino]-4-(4-oxidanyl-4-oxidanylidene-butyl)-2,3-dihydro-1,4-benzoxazine-2-carboxylic+acid'>KO5</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</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=6rz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rz9 OCA], [https://pdbe.org/6rz9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rz9 RCSB], [https://www.ebi.ac.uk/pdbsum/6rz9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rz9 ProSAT]</span></td></tr>
 </table>

6rz9

From Proteopedia

Current revision

Crystal structure of the human cysteinyl leukotriene receptor 2 in complex with ONO-2770372

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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