This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6rz4

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 11:07, 30 March 2022

Crystal structure of cysteinyl leukotriene receptor 1 in complex with pranlukast

Structural highlights

6rz4 is a 1 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	CYSLTR1, CYSLT1 ("Bacillus coli" Migula 1895)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

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^[1]

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

References

↑ 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. Structure-based mechanism of cysteinyl leukotriene receptor inhibition by antiasthmatic drugs. Sci Adv. 2019 Oct 9;5(10):eaax2518. doi: 10.1126/sciadv.aax2518. eCollection 2019, Oct. PMID:31633023 doi:http://dx.doi.org/10.1126/sciadv.aax2518

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6rz4"

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. 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 [http://proteopedia.org/fgij/fg.htm?mol=6RZ4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rz4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. 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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYSLTR1, CYSLT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYSLTR1, CYSLT1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rz4 OCA], [http://pdbe.org/6rz4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rz4 RCSB], [http://www.ebi.ac.uk/pdbsum/6rz4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rz4 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=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 ==
-[[http://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.
+[[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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

6rz4

From Proteopedia

Revision as of 11:07, 30 March 2022

Crystal structure of cysteinyl leukotriene receptor 1 in complex with pranlukast

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox