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3n7s

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{{STRUCTURE_3n7s| PDB=3n7s | SCENE= }}
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==Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals the site of drug antagonism==
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===Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals the site of drug antagonism===
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<StructureSection load='3n7s' size='340' side='right' caption='[[3n7s]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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{{ABSTRACT_PUBMED_20826335}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3n7s]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N7S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N7S FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3N6:N-{(1S)-5-AMINO-1-[(4-PYRIDIN-4-YLPIPERAZIN-1-YL)CARBONYL]PENTYL}-3,5-DIBROMO-NALPHA-{[4-(2-OXO-1,4-DIHYDROQUINAZOLIN-3(2H)-YL)PIPERIDIN-1-YL]CARBONYL}-D-TYROSINAMIDE'>3N6</scene>, <scene name='pdbligand=3N7:N~4~-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)-N~2~-1H-INDAZOL-5-YL-6-METHYLPYRIMIDINE-2,4-DIAMINE'>3N7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n7p|3n7p]], [[3n7r|3n7r]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALCRL, CALRL_HUMAN, CGRPR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), RAMP1, RAMP1_HUMAN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=3n7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n7s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n7s RCSB], [http://www.ebi.ac.uk/pdbsum/3n7s PDBsum]</span></td></tr>
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</table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n7/3n7s_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Dysregulation of the calcitonin gene-related peptide (CGRP), a potent vasodilator, is directly implicated in the pathogenesis of migraine. CGRP binds to and signals through the CGRP receptor (CGRP-R), a heterodimer containing the calcitonin receptor-like receptor (CLR), a class B GPCR, and RAMP1, a receptor activity-modifying protein. We have solved the crystal structure of the CLR/RAMP1 N-terminal ectodomain heterodimer, revealing how RAMPs bind to and potentially modulate the activities of the CLR GPCR subfamily. We also report the structures of CLR/RAMP1 in complex with the clinical receptor antagonists olcegepant (BIBN4096BS) and telcagepant (MK0974). Both drugs act by blocking access to the peptide-binding cleft at the interface of CLR and RAMP1. These structures illustrate, for the first time, how small molecules bind to and modulate the activity of a class B GPCR, and highlight the challenges of designing potent receptor antagonists for the treatment of migraine and other class B GPCR-related diseases.
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==Function==
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Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism.,ter Haar E, Koth CM, Abdul-Manan N, Swenson L, Coll JT, Lippke JA, Lepre CA, Garcia-Guzman M, Moore JM Structure. 2010 Sep 8;18(9):1083-93. PMID:20826335<ref>PMID:20826335</ref>
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[[http://www.uniprot.org/uniprot/RAMP1_HUMAN RAMP1_HUMAN]] Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL.<ref>PMID:9620797</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3n7s]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N7S OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020826335</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Haar, E Ter.]]
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[[Category: Haar, E Ter]]
[[Category: Antagonist]]
[[Category: Antagonist]]
[[Category: Class b gpcr]]
[[Category: Class b gpcr]]

Revision as of 15:11, 18 December 2014

Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals the site of drug antagonism

3n7s, resolution 2.10Å

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