5nx2: Difference between revisions
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New page: '''Unreleased structure''' The entry 5nx2 is ON HOLD Authors: Rappas, M., Jazayeri, A., Brown, A.J.H., Kean, J., Errey, J.C., Robertson, N., Fiez-Vandal, C., Andrews, S.P., Congreve, M.... |
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The | ==Crystal structure of thermostabilised full-length GLP-1R in complex with a truncated peptide agonist at 3.7 A resolution== | ||
<StructureSection load='5nx2' size='340' side='right'caption='[[5nx2]], [[Resolution|resolution]] 3.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5nx2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NX2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9DK:3-[2-(1~{H}-imidazol-4-yl)ethylamino]-2,2-dimethyl-3-oxidanylidene-propanoic+acid'>9DK</scene>, <scene name='pdbligand=9DQ:(2~{S})-2-azanyl-3-(1~{H}-1,2,3,4-tetrazol-5-yl)propanoic+acid'>9DQ</scene>, <scene name='pdbligand=9DT:(2~{S})-2-azanyl-3-(2-fluorophenyl)-2-methyl-propanoic+acid'>9DT</scene>, <scene name='pdbligand=9DW:(2~{S})-2-azanyl-3-[4-(2-ethyl-4-methoxy-phenyl)phenyl]propanoic+acid'>9DW</scene>, <scene name='pdbligand=9DZ:(2~{S})-2-azanyl-5-(3,5-dimethylphenyl)pentanamide'>9DZ</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SOG:2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL'>SOG</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=5nx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nx2 OCA], [https://pdbe.org/5nx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nx2 RCSB], [https://www.ebi.ac.uk/pdbsum/5nx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nx2 ProSAT]</span></td></tr> | |||
</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 == | |||
Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an alpha-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors. Guided by this structural information, we design peptide agonists with potent in vivo activity in a mouse model of diabetes. | |||
Crystal structure of the GLP-1 receptor bound to a peptide agonist.,Jazayeri A, Rappas M, Brown AJH, Kean J, Errey JC, Robertson NJ, Fiez-Vandal C, Andrews SP, Congreve M, Bortolato A, Mason JS, Baig AH, Teobald I, Dore AS, Weir M, Cooke RM, Marshall FH Nature. 2017 Jun 8;546(7657):254-258. doi: 10.1038/nature22800. Epub 2017 May 31. PMID:28562585<ref>PMID:28562585</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5nx2" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Baig | ==See Also== | ||
[[Category: | *[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Fiez-Vandal | [[Category: Large Structures]] | ||
[[Category: Kean | [[Category: Synthetic construct]] | ||
[[Category: Marshall | [[Category: Andrews SP]] | ||
[[Category: | [[Category: Baig AH]] | ||
[[Category: | [[Category: Bortolato A]] | ||
[[Category: | [[Category: Brown AJH]] | ||
[[Category: | [[Category: Congreve M]] | ||
[[Category: | [[Category: Cooke RM]] | ||
[[Category: Dore AS]] | |||
[[Category: Errey JC]] | |||
[[Category: Fiez-Vandal C]] | |||
[[Category: Jazayeri A]] | |||
[[Category: Kean J]] | |||
[[Category: Marshall FH]] | |||
[[Category: Mason JS]] | |||
[[Category: Rappas M]] | |||
[[Category: Robertson N]] | |||
[[Category: Teobald I]] | |||
[[Category: Weir M]] | |||
Latest revision as of 12:52, 15 November 2023
Crystal structure of thermostabilised full-length GLP-1R in complex with a truncated peptide agonist at 3.7 A resolutionCrystal structure of thermostabilised full-length GLP-1R in complex with a truncated peptide agonist at 3.7 A resolution
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 PubMedGlucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an alpha-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors. Guided by this structural information, we design peptide agonists with potent in vivo activity in a mouse model of diabetes. Crystal structure of the GLP-1 receptor bound to a peptide agonist.,Jazayeri A, Rappas M, Brown AJH, Kean J, Errey JC, Robertson NJ, Fiez-Vandal C, Andrews SP, Congreve M, Bortolato A, Mason JS, Baig AH, Teobald I, Dore AS, Weir M, Cooke RM, Marshall FH Nature. 2017 Jun 8;546(7657):254-258. doi: 10.1038/nature22800. Epub 2017 May 31. PMID:28562585[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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