3FJD
Crystal structure of L44F/F132W mutant of Human acidic fibroblast growth factor
Summary for 3FJD
| Entry DOI | 10.2210/pdb3fjd/pdb |
| Related | 1JQZ 3FGM 3FJ8 3FJ9 3FJA 3FJB 3FJC 3FJE 3FJF 3FJH 3FJI 3FJJ 3FJK |
| Descriptor | Heparin-binding growth factor 1, SULFATE ION, FORMIC ACID, ... (4 entities in total) |
| Functional Keywords | beta-trefoil, acetylation, angiogenesis, developmental protein, differentiation, growth factor, heparin-binding, mitogen, polymorphism, hormone |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: P05230 |
| Total number of polymer chains | 2 |
| Total formula weight | 33753.74 |
| Authors | Blaber, M.,Lee, J. (deposition date: 2008-12-14, release date: 2009-10-06, Last modification date: 2023-09-06) |
| Primary citation | Lee, J.,Blaber, M. The interaction between thermodynamic stability and buried free cysteines in regulating the functional half-life of fibroblast growth factor-1. J.Mol.Biol., 393:113-127, 2009 Cited by PubMed Abstract: Protein biopharmaceuticals are an important and growing area of human therapeutics; however, the intrinsic property of proteins to adopt alternative conformations (such as during protein unfolding and aggregation) presents numerous challenges, limiting their effective application as biopharmaceuticals. Using fibroblast growth factor-1 as model system, we describe a cooperative interaction between the intrinsic property of thermostability and the reactivity of buried free-cysteine residues that can substantially modulate protein functional half-life. A mutational strategy that combines elimination of buried free cysteines and secondary mutations that enhance thermostability to achieve a substantial gain in functional half-life is described. Furthermore, the implementation of this design strategy utilizing stabilizing mutations within the core region resulted in a mutant protein that is essentially indistinguishable from wild type as regard protein surface and solvent structure, thus minimizing the immunogenic potential of the mutations. This design strategy should be generally applicable to soluble globular proteins containing buried free-cysteine residues. PubMed: 19695265DOI: 10.1016/j.jmb.2009.08.026 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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