6zho
From Proteopedia
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==Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor== | ==Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor== | ||
| - | <StructureSection load='6zho' size='340' side='right'caption='[[6zho]]' scene=''> | + | <StructureSection load='6zho' size='340' side='right'caption='[[6zho]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZHO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZHO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6zho]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZHO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZHO FirstGlance]. <br> |
| - | </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=6zho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zho OCA], [http://pdbe.org/6zho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zho RCSB], [http://www.ebi.ac.uk/pdbsum/6zho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zho ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=QLQ:~{N}-[(2~{R})-3-(7-methyl-2~{H}-indazol-5-yl)-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-piperidin-4-yl-1-(4-pyridin-4-ylpiperazin-1-yl)propan-2-yl]amino]propan-2-yl]-2-oxidanylidene-spiro[1~{H}-pyrido[2,3-d][1,3]oxazine-4,4-piperidine]-1-carboxamide'>QLQ</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALCRL, CGRPR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6zho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zho OCA], [http://pdbe.org/6zho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zho RCSB], [http://www.ebi.ac.uk/pdbsum/6zho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zho ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Structure-based drug design enabled the discovery of 8, HTL22562, a calcitonin gene-related peptide (CGRP) receptor antagonist. The structure of 8 complexed with the CGRP receptor was determined at a 1.6 A resolution. Compound 8 is a highly potent, selective, metabolically stable, and soluble compound suitable for a range of administration routes that have the potential to provide rapid systemic exposures with resultant high levels of receptor coverage (e.g., subcutaneous). The low lipophilicity coupled with a low anticipated clinically efficacious plasma exposure for migraine also suggests a reduced potential for hepatotoxicity. These properties have led to 8 being selected as a clinical candidate for acute treatment of migraine. | ||
| + | |||
| + | Structure-Based Drug Discovery of N-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-( pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2'-oxo-1',2'-dihydrosp iro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine.,Bucknell SJ, Ator MA, Brown AJH, Brown J, Cansfield AD, Cansfield JE, Christopher JA, Congreve M, Cseke G, Deflorian F, Jones CR, Mason JS, O'Brien MA, Ott GR, Pickworth M, Southall SM J Med Chem. 2020 Jul 8. doi: 10.1021/acs.jmedchem.0c01003. PMID:32558564<ref>PMID:32558564</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6zho" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Southall | + | [[Category: Southall, S M]] |
| + | [[Category: Cgrp]] | ||
| + | [[Category: Clr]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Ecd]] | ||
| + | [[Category: Gpcr]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Ramp1]] | ||
Revision as of 06:00, 5 August 2020
Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor
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Categories: Human | Large Structures | Southall, S M | Cgrp | Clr | Complex | Ecd | Gpcr | Membrane protein | Ramp1
