Role of the sulfur to α-carbon thioether bridges in thurincin H

Magdalena Mozolewska , Adam Sieradzan , Andrei Niadzvedtski , Cezary Czaplewski , Józef Adam Liwo , Paweł Krupa


Thurincin H is a small protein produced by Bacillus thuringiensis SF361 with gram-positive antimicrobial properties. The toxins produced by B. thuringiensis are widely used in the agriculture as, e.g. natural preservatives in dairy products. The structure of thurincin H possesses four covalent sulfur to -carbon bonds that involve the cysteine side-chains; these bonds are probably responsible for the shape and stability of the protein and, thereby, for its antimicrobial properties. To examine the influence of the formation of the sulfur-carbon bonds on the folding pathways and stability of the protein, a series of canonical and multiplexed replica-exchange simulations with the coarse-grained UNRES force field was carried out without and with distance restraints imposed on selected S-C atom pairs. It was found that the order of the formation and breaking of the S-C thioether bonds significantly impacts on the foldability and stability of the thurincin H. It was also observed that thioether bridges play a major role in stabilizing the global fold of the protein, although it significantly diminishes the entropy of the system. The maximum foldability of thurincin H was observed in the presence of the optimal set of three out of four thioether bridges. Thus, the results suggest that the presence of ThnB enzyme and other agents that catalyze the formation of thioether bridges can be essential for correct folding of thurincin H and that the formation of the fourth bridge does not seem to facilitate folding; instead, it seems to rigidify the loop and prevent proteolysis.
Author Magdalena Mozolewska PMM
Magdalena Mozolewska,,
- Laboratory of Molecular Modeling
, Adam Sieradzan PMM
Adam Sieradzan,,
- Laboratory of Molecular Modeling
, Andrei Niadzvedtski PK
Andrei Niadzvedtski ,,
- Pracownia Krystalochemii
, Cezary Czaplewski PSP
Cezary Czaplewski,,
- Laboratory of Simulation of Polymers
, Józef Adam Liwo PMM
Józef Adam Liwo,,
- Laboratory of Molecular Modeling
, Paweł Krupa PSP
Paweł Krupa,,
- Laboratory of Simulation of Polymers
Journal seriesJournal of Biomolecular Structure & Dynamics, ISSN 0739-1102
Issue year2017
Publication size in sheets0.55
Keywords in Englishprotein folding, thermal stability, molecular dynamics simulations, UNRES force field, sactipeptide
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 20.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 3.123 (2) - 2016=2.555 (5)
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