View source for 9g5p


==Trp-cage fortified Tc5b-Exenatide chimera (Ex4-Tc5bER) at 277K==
<StructureSection load='9g5p' size='340' side='right'caption='[[9g5p]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9g5p]] 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=9G5P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9G5P FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</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=9g5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9g5p OCA], [https://pdbe.org/9g5p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9g5p RCSB], [https://www.ebi.ac.uk/pdbsum/9g5p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9g5p 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 ==
Exenatide (Ex4), a GLP-1 incretin mimetic polypeptide, is an effective therapeutic agent against diabetes and obesity. We highlight the indirect role of Ex4's structure-stabilizing Trp-cage (Tc) motif in governing GLP-1 receptor (GLP-1R) signal transduction. We use various Ex4 derivatives to explore how Tc compactness influences thermal stability, aggregation, enhancement of insulin secretion, and GLP-1R binding. We found that Ex4 variants decorated with fortified Tc motifs exhibit increased resistance to unfolding and aggregation but show an inverse relationship between the bioactivity and stability. Molecular dynamics simulations coupled with a rigid-body segmentation protocol to analyze dynamic interconnectedness revealed that the constrained Tc motifs remain intact within the receptor-ligand complexes but interfere with one of the major stabilizing contacts and recognition loci on the extracellular side of GLP-1R, dislodging the N-terminal activating region of the hormone mimetics, and restrict the free movement of TM6, the main signal transduction device of GLP-1R.

Influence of Trp-Cage on the Function and Stability of GLP-1R Agonist Exenatide Derivatives.,Horvath D, Straner P, Taricska N, Fazekas Z, Menyhard DK, Perczel A J Med Chem. 2024 Sep 10. doi: 10.1021/acs.jmedchem.4c01553. PMID:39254428<ref>PMID:39254428</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9g5p" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Heloderma suspectum]]
[[Category: Large Structures]]
[[Category: Horvath D]]