7lci
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[7lci]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCI FirstGlance]. <br> | <table><tr><td colspan='2'>[[7lci]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LCI FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UK4:2-[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UK4:2-[[4-[6-[(4-cyano-2-fluoranyl-phenyl)methoxy]pyridin-2-yl]piperidin-1-yl]methyl]-3-[[(2~{S})-oxetan-2-yl]methyl]benzimidazole-5-carboxylic+acid'>UK4</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=7lci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lci OCA], [https://pdbe.org/7lci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lci RCSB], [https://www.ebi.ac.uk/pdbsum/7lci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lci 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=7lci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lci OCA], [https://pdbe.org/7lci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lci RCSB], [https://www.ebi.ac.uk/pdbsum/7lci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lci ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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G protein-coupled receptors (GPCRs) are the largest class of cell surface drug targets. Advances in stabilization of GPCR:transducer complexes, together with improvements in cryoelectron microscopy (cryo-EM) have recently been applied to structure-assisted drug design for GPCR agonists. Nonetheless, limitations in the commercial application of these approaches, including the use of nanobody 35 (Nb35) to aid complex stabilization and the high cost of 300 kV imaging, have restricted broad application of cryo-EM in drug discovery. Here, using the PF 06882961-bound GLP-1R as exemplar, we validated the formation of stable complexes with a modified Gs protein in the absence of Nb35. In parallel, we compare 200 versus 300 kV image acquisition using a Falcon 4 or K3 direct electron detector. Moreover, the 200 kV Glacios-Falcon 4 yielded a 3.2 A map with clear density for bound drug and multiple structurally ordered waters. Our work paves the way for broader commercial application of cryo-EM for GPCR drug discovery. | G protein-coupled receptors (GPCRs) are the largest class of cell surface drug targets. Advances in stabilization of GPCR:transducer complexes, together with improvements in cryoelectron microscopy (cryo-EM) have recently been applied to structure-assisted drug design for GPCR agonists. Nonetheless, limitations in the commercial application of these approaches, including the use of nanobody 35 (Nb35) to aid complex stabilization and the high cost of 300 kV imaging, have restricted broad application of cryo-EM in drug discovery. Here, using the PF 06882961-bound GLP-1R as exemplar, we validated the formation of stable complexes with a modified Gs protein in the absence of Nb35. In parallel, we compare 200 versus 300 kV image acquisition using a Falcon 4 or K3 direct electron detector. Moreover, the 200 kV Glacios-Falcon 4 yielded a 3.2 A map with clear density for bound drug and multiple structurally ordered waters. Our work paves the way for broader commercial application of cryo-EM for GPCR drug discovery. | ||
| - | + | , PMID:33957078<ref>PMID:33957078</ref> | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
PF 06882961 bound to the glucagon-like peptide-1 receptor (GLP-1R):Gs complex
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Categories: Homo sapiens | Large Structures | Belousoff MJ | Danev R | Drulyte I | Johnson RM | Kotecha A | Sexton PM | Wootten D | Yu L | Zhang X
