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==Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile== | ==Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile== | ||
<StructureSection load='5cgc' size='340' side='right' caption='[[5cgc]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='5cgc' size='340' side='right'caption='[[5cgc]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5cgc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CGC FirstGlance]. <br> | <table><tr><td colspan='2'>[[5cgc]] 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=5CGC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CGC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=51D:3-CHLORO-4-FLUORO-5-[6-(1H-PYRAZOL-1-YL)PYRIMIDIN-4-YL]BENZONITRILE'>51D</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=51D:3-CHLORO-4-FLUORO-5-[6-(1H-PYRAZOL-1-YL)PYRIMIDIN-4-YL]BENZONITRILE'>51D</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oo9|4oo9]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oo9|4oo9]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRM5, GPRC1E, MGLUR5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr> | ||
<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=5cgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgc OCA], [http://pdbe.org/5cgc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cgc RCSB], [http://www.ebi.ac.uk/pdbsum/5cgc PDBsum]</span></td></tr> | <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=5cgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgc OCA], [http://pdbe.org/5cgc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cgc RCSB], [http://www.ebi.ac.uk/pdbsum/5cgc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cgc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5cgc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5cgc" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Metabotropic glutamate receptor|Metabotropic glutamate receptor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Lysozyme]] | [[Category: Lysozyme]] | ||
[[Category: Aves, S J]] | [[Category: Aves, S J]] | ||
Revision as of 10:33, 24 April 2019
Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrileStructure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile
Structural highlights
Function[GRM5_HUMAN] Receptor for glutamate. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Publication Abstract from PubMedFragment screening of a thermostabilized mGlu5 receptor using a high-concentration radioligand binding assay enabled the identification of moderate affinity, high ligand efficiency (LE) pyrimidine hit 5. Subsequent optimization using structure-based drug discovery methods led to the selection of 22, HTL14242, as an advanced lead compound for further development. Structures of the stabilized mGlu5 receptor complexed with 22 and another molecule in the series, 11, were determined at resolutions of 2.6A and 3.1A respectively. Fragment and Structure-Based Drug Discovery for a Class C GPCR: Discovery of the mGlu5 negative allosteric modulator HTL14242 (3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile).,Christopher J, Aves SJ, Bennett KA, Dore AS, Errey JC, Jazayeri A, Marshall FH, Okrasa K, Serrano-Vega MJ, Tehan B, Wiggin GR, Congreve M J Med Chem. 2015 Jul 30. PMID:26225459[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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