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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6401

Narzi, D; Siu, S W I; Stirnimann, C U; Grimshaw, J P A; Glockshuber, R; Capitani, G; Böckmann, R A (2008). Evidence for proton shuffling in a thioredoxin-like protein during catalysis. Journal of Molecular Biology, 382(4):978-986.

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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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biochemistry
07 Faculty of Science > Institute of Biochemistry
DDC:570 Life sciences; biology
Date:17 October 2008
Deposited On:18 Dec 2008 11:51
Last Modified:28 Nov 2013 00:58
Publisher DOI:10.1016/j.jmb.2008.07.061
PubMed ID:18692066
Citations:Web of Science®. Times Cited: 3
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