4X43

Structure of proline-free E. coli Thioredoxin

4X43 の概要

• エントリーDOI: 10.2210/pdb4x43/pdb
• 分子名称: Thioredoxin-1 (2 entities in total)
• 機能のキーワード: protein folding, thioredoxin fold, protein disulfide oxidoreductase activity, redox protein, oxidoreductase
• 由来する生物種: Escherichia coli K-12
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 34671.60

構造登録者

Scharer, M.A.,Glockshuber, R. (登録日: 2014-12-02, 公開日: 2015-06-24, 最終更新日: 2024-10-16)

主引用文献

Roderer, D.J.,Scharer, M.A.,Rubini, M.,Glockshuber, R.
Acceleration of protein folding by four orders of magnitude through a single amino acid substitution.
Sci Rep, 5:11840-11840, 2015

PubMed Abstract: Cis prolyl peptide bonds are conserved structural elements in numerous protein families, although their formation is energetically unfavorable, intrinsically slow and often rate-limiting for folding. Here we investigate the reasons underlying the conservation of the cis proline that is diagnostic for the fold of thioredoxin-like thiol-disulfide oxidoreductases. We show that replacement of the conserved cis proline in thioredoxin by alanine can accelerate spontaneous folding to the native, thermodynamically most stable state by more than four orders of magnitude. However, the resulting trans alanine bond leads to small structural rearrangements around the active site that impair the function of thioredoxin as catalyst of electron transfer reactions by more than 100-fold. Our data provide evidence for the absence of a strong evolutionary pressure to achieve intrinsically fast folding rates, which is most likely a consequence of proline isomerases and molecular chaperones that guarantee high in vivo folding rates and yields.

PubMed: 26121966
DOI: 10.1038/srep11840

実験手法

X-RAY DIFFRACTION (1.65 Å)