9gdu
From Proteopedia
(Difference between revisions)
m (Protected "9gdu" [edit=sysop:move=sysop]) |
|||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Trp-cage fortified Tc5b-Exenatide chimera with disulfide bond cyclization (Ex-4-Tc5bCC) at 310K== | |
| + | <StructureSection load='9gdu' size='340' side='right'caption='[[9gdu]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9gdu]] 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=9GDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9GDU 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=9gdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9gdu OCA], [https://pdbe.org/9gdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9gdu RCSB], [https://www.ebi.ac.uk/pdbsum/9gdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9gdu ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Horvath | + | <div class="pdbe-citations 9gdu" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Heloderma suspectum]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Horvath D]] | ||
Current revision
Trp-cage fortified Tc5b-Exenatide chimera with disulfide bond cyclization (Ex-4-Tc5bCC) at 310K
| |||||||||||
