4X43

Structure of proline-free E. coli Thioredoxin

Summary for 4X43

• Entry DOI: 10.2210/pdb4x43/pdb
• Descriptor: Thioredoxin-1 (2 entities in total)
• Functional Keywords: protein folding, thioredoxin fold, protein disulfide oxidoreductase activity, redox protein, oxidoreductase
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 3
• Total formula weight: 34671.60

Authors

Scharer, M.A.,Glockshuber, R. (deposition date: 2014-12-02, release date: 2015-06-24, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.65 Å)