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5niq
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==exendin-4 variant with dual GLP-1 / glucagon receptor activity== | |
| + | <StructureSection load='5niq' size='340' side='right'caption='[[5niq]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5niq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Heloderma_suspectum Heloderma suspectum]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NIQ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D6M:N-HEXADECANOYL-L-GLUTAMIC+ACID'>D6M</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=5niq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5niq OCA], [https://pdbe.org/5niq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5niq RCSB], [https://www.ebi.ac.uk/pdbsum/5niq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5niq ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/EXE4_HELSU EXE4_HELSU] Venom protein that mimics the incretin hormone glucagon-like peptide 1 (GLP-1). It stimulates insulin synthesis and secretion, protects against beta-cell apoptosis in response to different insults, and promotes beta-cell proliferation. It also promotes satiety, reduces food intake, reduces fat deposition, reduces body weight and inhibits gastric emptying. Interacts with GLP-1 receptor (GLP1R). Induces hypotension that is mediated by relaxation of cardiac smooth muscle.<ref>PMID:8405712</ref> <ref>PMID:19837656</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Dual activation of the glucagon-like peptide 1 (GLP-1) and glucagon receptor has the potential to lead to a novel therapy principle for the treatment of diabesity. Here, we report a series of novel peptides with dual activity on these receptors that were discovered by rational design. On the basis of sequence analysis and structure-based design, structural elements of glucagon were engineered into the selective GLP-1 receptor agonist exendin-4, resulting in hybrid peptides with potent dual GLP-1/glucagon receptor activity. Detailed structure-activity relationship data are shown. Further modifications with unnatural and modified amino acids resulted in novel metabolically stable peptides that demonstrated a significant dose-dependent decrease in blood glucose in chronic studies in diabetic db/db mice and reduced body weight in diet-induced obese (DIO) mice. Structural analysis by NMR spectroscopy confirmed that the peptides maintain an exendin-4-like structure with its characteristic tryptophan-cage fold motif that is responsible for favorable chemical and physical stability. | ||
| - | + | Design of Novel Exendin-Based Dual Glucagon-like Peptide 1 (GLP-1)/Glucagon Receptor Agonists.,Evers A, Haack T, Lorenz M, Bossart M, Elvert R, Henkel B, Stengelin S, Kurz M, Glien M, Dudda A, Lorenz K, Kadereit D, Wagner M J Med Chem. 2017 May 25;60(10):4293-4303. doi: 10.1021/acs.jmedchem.7b00174. Epub, 2017 May 5. PMID:28448133<ref>PMID:28448133</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5niq" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Heloderma suspectum]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Evers A]] | ||
| + | [[Category: Kurz M]] | ||
Current revision
exendin-4 variant with dual GLP-1 / glucagon receptor activity
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