4zgm
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4zgm is ON HOLD until Paper Publication Authors: Reedtz-Runge, S. Description: Crystal structure of Semaglutide peptide backbone in complex with th...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Semaglutide peptide backbone in complex with the GLP-1 receptor extracellular domain== | |
| + | <StructureSection load='4zgm' size='340' side='right'caption='[[4zgm]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4zgm]] is a 2 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=4ZGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZGM 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32M:3,6,9,12,15,18-HEXAOXAHEXACOSAN-1-OL'>32M</scene>, <scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</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=4zgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zgm OCA], [https://pdbe.org/4zgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zgm RCSB], [https://www.ebi.ac.uk/pdbsum/4zgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zgm 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 == | ||
| + | Liraglutide is an acylated Glucagon-Like Peptide-1 (GLP-1) analog that binds to serum albumin in vivo, and is approved for once daily treatment of diabetes as well as obesity. The aim of the present studies was to design a once-weekly GLP-1 analog by increasing albumin affinity and secure full stability against metabolic degradation. The fatty acid moiety and the linking chemistry to GLP-1 were the key features to secure high albumin affinity and GLP-1 receptor (GLP-1R) potency and in obtaining a prolonged exposure and action of the GLP-1 analog. Semaglutide was selected as the optimal once weekly candidate. Semaglutide has two amino acid substitutions compared to human GLP-1 (Aib8, Arg34) and is derivatized at lysine 26. The GLP-1R affinity of semaglutide (0.38 +/- 0.06 nM) was 3-fold decreased compared to liraglutide, whereas the albumin affinity was increased. The plasma half-life was 46h in mini-pigs following i.v. administration and semaglutide has an MRT of 63.6h after s.c. dosing. Semaglutide is currently in phase 3 clinical testing. | ||
| - | + | The discovery of the once weekly glucagon like peptide 1 (GLP-1) analog semaglutide.,Lau J, Bloch P, Schaffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T J Med Chem. 2015 Aug 26. PMID:26308095<ref>PMID:26308095</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Reedtz-Runge | + | <div class="pdbe-citations 4zgm" style="background-color:#fffaf0;"></div> |
| + | |||
| + | ==See Also== | ||
| + | *[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Reedtz-Runge S]] | ||
Current revision
Crystal structure of Semaglutide peptide backbone in complex with the GLP-1 receptor extracellular domain
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