6M6F
Solution structure of disulfide bond mutaion of the core domain of Fibroblast growth factor 21 (FGF21)
Summary for 6M6F
| Entry DOI | 10.2210/pdb6m6f/pdb |
| Related | 6M6E |
| Descriptor | Fibroblast growth factor 21 (1 entity in total) |
| Functional Keywords | disulfide bond mutaion, beta-trefoil conformation, beta-klotho binding, metabolic regulator, hormone |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14103.98 |
| Authors | |
| Primary citation | 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. Dynamic folding modulation generates FGF21 variant against diabetes. Embo Rep., 22:e51352-e51352, 2021 Cited by PubMed Abstract: 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 β-trefoil conformation affects the folding of β2-β3 hairpin and further overall protein stability. To modulate folding dynamics, we designed an FGF21-FGF19 chimera, FGF21 . As expected, FGF21 shows better thermostability without inducing hepatocyte proliferation. Functional characterization of FGF21 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. PubMed: 33295692DOI: 10.15252/embr.202051352 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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