Evidence for proton shuffling in a thioredoxin-like protein during catalysis.

Narzi D, Siu SWI, Stirnimann CU, Grimshaw JPA, Glockshuber R, Capitani G, Böckmann R (2008)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2008

Journal

Journal of Molecular Biology Elsevier

Book Volume: 382

Pages Range: 978-86

Volume: 382

Issue: 4

Journal Issue: 4

DOI: 10.1016/j.jmb.2008.07.061

Abstract

Proteins of the thioredoxin (Trx) superfamily catalyze disulfide-bond formation, reduction and isomerization in substrate proteins both in prokaryotic and in eukaryotic cells. All members of the Trx family with thiol-disulfide oxidoreductase activity contain the characteristic Cys-X-X-Cys motif in their active site. Here, using Poisson-Boltzmann-based protonation-state calculations based on 100-ns molecular dynamics simulations, we investigate the catalytic mechanism of DsbL, the most oxidizing Trx-like protein known to date. We observed several correlated transitions in the protonation states of the buried active-site cysteine and a neighboring lysine coupled to the exposure of the active-site thiolate. These results support the view of an internal proton shuffling mechanism during oxidation crucial for the uptake of two electrons from the substrate protein. Intramolecular disulfide-bond formation is probably steered by the conformational switch facilitating interaction with the active-site thiolate. A consistent catalytic mechanism for DsbL, probably conferrable to other proteins of the same class, is presented. Our results suggest a functional role of hydration entropy of active-site groups.

Authors with CRIS profile

Daniele Narzi Professur für Computational Biology Shirley Weng In Siu Professur für Computational Biology Rainer Böckmann Professur für Computational Biology

Involved external institutions

University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH)

How to cite

APA:

Narzi, D., Siu, S.W.I., Stirnimann, C.U., Grimshaw, J.P.A., Glockshuber, R., Capitani, G., & Böckmann, R. (2008). Evidence for proton shuffling in a thioredoxin-like protein during catalysis. Journal of Molecular Biology, 382(4), 978-86. https://doi.org/10.1016/j.jmb.2008.07.061

MLA:

Narzi, Daniele, et al. "Evidence for proton shuffling in a thioredoxin-like protein during catalysis." Journal of Molecular Biology 382.4 (2008): 978-86.

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