6m6e
From Proteopedia
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<StructureSection load='6m6e' size='340' side='right'caption='[[6m6e]]' scene=''> | <StructureSection load='6m6e' size='340' side='right'caption='[[6m6e]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full | + | <table><tr><td colspan='2'>Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M6E FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </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=6m6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m6e OCA], [https://pdbe.org/6m6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m6e RCSB], [https://www.ebi.ac.uk/pdbsum/6m6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m6e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fibroblast growth factor 21 (FGF21) is a regulator of glucose and lipid metabolism. It has been widely considered as a promising candidate for the treatment of type 2 diabetes mellitus (T2DM) and other related metabolic disorders. However, lack of structural and dynamic information has limited FGF21-based drug development. Here, using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of FGF21 and find that its non-canonical flexible beta-trefoil conformation affects the folding of beta2-beta3 hairpin and further overall protein stability. To modulate folding dynamics, we designed an FGF21-FGF19 chimera, FGF21(SS) . As expected, FGF21(SS) shows better thermostability without inducing hepatocyte proliferation. Functional characterization of FGF21(SS) shows its better insulin sensitivity, reduced inflammation in 3T3-L1 adipocytes, and lower blood glucose and insulin levels in ob/ob mice compared with wild type. Our dynamics-based rational design provides a promising approach for FGF21-based therapeutic development against T2DM. | ||
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| + | Dynamic folding modulation generates FGF21 variant against diabetes.,Zhu L, Zhao H, Liu J, Cai H, Wu B, Liu Z, Zhou S, Liu Q, Li X, Bao B, Liu J, Dai H, Wang J EMBO Rep. 2020 Dec 9:e51352. doi: 10.15252/embr.202051352. PMID:33295692<ref>PMID:33295692</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6m6e" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Solution structure of the core domain of Fibroblast growth factor 21 (FGF21)
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Categories: Large Structures | Wang J | Zhao H | Zhu L
