7lci: Difference between revisions
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==== | ==PF 06882961 bound to the glucagon-like peptide-1 receptor (GLP-1R):Gs complex== | ||
<StructureSection load='7lci' size='340' side='right'caption='[[7lci]]' scene=''> | <StructureSection load='7lci' size='340' side='right'caption='[[7lci]], [[Resolution|resolution]] 2.90Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= 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='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> | </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-[(4-{6-[(4-cyano-2-fluorophenyl)methoxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-{[(2S)-oxetan-2-yl]methyl}-1H-benzimidazole-6-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> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/GLP1R_HUMAN GLP1R_HUMAN] This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Evolving cryo-EM structural approaches for GPCR drug discovery.,Zhang X, Johnson RM, Drulyte I, Yu L, Kotecha A, Danev R, Wootten D, Sexton PM, Belousoff MJ Structure. 2021 May 2. pii: S0969-2126(21)00124-6. doi:, 10.1016/j.str.2021.04.008. PMID:33957078<ref>PMID:33957078</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7lci" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Belousoff MJ]] | ||
[[Category: Danev R]] | |||
[[Category: Drulyte I]] | |||
[[Category: Johnson RM]] | |||
[[Category: Kotecha A]] | |||
[[Category: Sexton PM]] | |||
[[Category: Wootten D]] | |||
[[Category: Yu L]] | |||
[[Category: Zhang X]] | |||
Latest revision as of 14:08, 23 October 2024
PF 06882961 bound to the glucagon-like peptide-1 receptor (GLP-1R):Gs complexPF 06882961 bound to the glucagon-like peptide-1 receptor (GLP-1R):Gs complex
Structural highlights
FunctionGLP1R_HUMAN This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMedG 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. Evolving cryo-EM structural approaches for GPCR drug discovery.,Zhang X, Johnson RM, Drulyte I, Yu L, Kotecha A, Danev R, Wootten D, Sexton PM, Belousoff MJ Structure. 2021 May 2. pii: S0969-2126(21)00124-6. doi:, 10.1016/j.str.2021.04.008. PMID:33957078[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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