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==Solution structure of disulfide bond mutaion of the core domain of Fibroblast growth factor 21 (FGF21)==
<StructureSection load='6m6f' size='340' side='right'caption='[[6m6f]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M6F 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=6m6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m6f OCA], [https://pdbe.org/6m6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m6f RCSB], [https://www.ebi.ac.uk/pdbsum/6m6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m6f ProSAT]</span></td></tr>
</table>
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== 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Wang J]]
[[Category: Zhao H]]
[[Category: Zhu L]]