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| | ==Crystal structure of Semaglutide peptide backbone in complex with the GLP-1 receptor extracellular domain== | | ==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=''> | + | <StructureSection load='4zgm' size='340' side='right'caption='[[4zgm]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zgm]] is a 2 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=4ZGM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZGM FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=32M:3,6,9,12,15,18-HEXAOXAHEXACOSAN-1-OL'>32M</scene></td></tr> | + | </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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3iol|3iol]]</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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLP1R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4zgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zgm OCA], [http://pdbe.org/4zgm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zgm RCSB], [http://www.ebi.ac.uk/pdbsum/4zgm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zgm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4zgm" style="background-color:#fffaf0;"></div> | | <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 == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Reedtz-Runge, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Complex]] | + | [[Category: Reedtz-Runge S]] |
| - | [[Category: Glp-1]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Signaling protein]]
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| Structural highlights
Function
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. The discovery of the once weekly glucagon like peptide 1 (GLP-1) analog semaglutide. J Med Chem. 2015 Aug 26. PMID:26308095 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00726
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