View source for 6rz4


==Crystal structure of cysteinyl leukotriene receptor 1 in complex with pranlukast==
<StructureSection load='6rz4' size='340' side='right'caption='[[6rz4]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rz4]] 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=6RZ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RZ4 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KNT:pranlukast'>KNT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6rz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rz4 OCA], [https://pdbe.org/6rz4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rz4 RCSB], [https://www.ebi.ac.uk/pdbsum/6rz4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rz4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/CLTR1_HUMAN CLTR1_HUMAN] Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 >> LTE4 = LTC4 >> LTB4.
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== Publication Abstract from PubMed ==
The G protein-coupled cysteinyl leukotriene receptor CysLT1R mediates inflammatory processes and plays a major role in numerous disorders, including asthma, allergic rhinitis, cardiovascular disease, and cancer. Selective CysLT1R antagonists are widely prescribed as antiasthmatic drugs; however, these drugs demonstrate low effectiveness in some patients and exhibit a variety of side effects. To gain deeper understanding into the functional mechanisms of CysLTRs, we determined the crystal structures of CysLT1R bound to two chemically distinct antagonists, zafirlukast and pranlukast. The structures reveal unique ligand-binding modes and signaling mechanisms, including lateral ligand access to the orthosteric pocket between transmembrane helices TM4 and TM5, an atypical pattern of microswitches, and a distinct four-residue-coordinated sodium site. These results provide important insights and structural templates for rational discovery of safer and more effective drugs.

Structure-based mechanism of cysteinyl leukotriene receptor inhibition by antiasthmatic drugs.,Luginina A, Gusach A, Marin E, Mishin A, Brouillette R, Popov P, Shiriaeva A, Besserer-Offroy E, Longpre JM, Lyapina E, Ishchenko A, Patel N, Polovinkin V, Safronova N, Bogorodskiy A, Edelweiss E, Hu H, Weierstall U, Liu W, Batyuk A, Gordeliy V, Han GW, Sarret P, Katritch V, Borshchevskiy V, Cherezov V Sci Adv. 2019 Oct 9;5(10):eaax2518. doi: 10.1126/sciadv.aax2518. eCollection 2019, Oct. PMID:31633023<ref>PMID:31633023</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rz4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Batyuk A]]
[[Category: Besserer-Offroy E]]
[[Category: Bogorodskiy A]]
[[Category: Borshchevskiy V]]
[[Category: Brouillette R]]
[[Category: Cherezov V]]
[[Category: Edelweiss E]]
[[Category: Gordeliy V]]
[[Category: Gusach A]]
[[Category: Han GW]]
[[Category: Ishchenko A]]
[[Category: Katritch V]]
[[Category: Liu W]]
[[Category: Longpre JM]]
[[Category: Luginina A]]
[[Category: Lyapina E]]
[[Category: Marin E]]
[[Category: Mishin A]]
[[Category: Patel N]]
[[Category: Polovinkin V]]
[[Category: Popov P]]
[[Category: Safronova N]]
[[Category: Sarret P]]
[[Category: Shiryaeva A]]