3FJA

Crystal structure of F132W mutant of Human acidic fibroblast growth factor

3FJA の概要

• エントリーDOI: 10.2210/pdb3fja/pdb
• 関連するPDBエントリー: 1JQZ 3FGM 3FJ8 3FJ9 3FJB 3FJC 3FJD 3FJE 3FJF 3FJH 3FJI 3FJJ 3FJK
• 分子名称: Heparin-binding growth factor 1, FORMIC ACID (3 entities in total)
• 機能のキーワード: beta-trefoil, acetylation, angiogenesis, developmental protein, differentiation, growth factor, heparin-binding, mitogen, polymorphism, hormone
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P05230
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33635.67

構造登録者

Blaber, M.,Lee, J. (登録日: 2008-12-14, 公開日: 2009-10-06, 最終更新日: 2023-09-06)

主引用文献

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

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: 19695265
DOI: 10.1016/j.jmb.2009.08.026

実験手法

X-RAY DIFFRACTION (1.95 Å)