The conserved active site tryptophan of thioredoxin has no effect on its redox properties.

TitleThe conserved active site tryptophan of thioredoxin has no effect on its redox properties.
Publication TypeJournal Article
Year of Publication2010
AuthorsRoos, G., P. Geerlings, and J. Messens
JournalProtein Sci
Volume19
Issue1
Pagination190-4
Date Published2010 Jan
Type of Articleredox
ISSN1469-896X
KeywordsCatalytic Domain, Conserved Sequence, Cysteine, Models, Molecular, Mutation, Oxidation-Reduction, Protein Stability, Staphylococcus aureus, Thioredoxins, Tryptophan
Abstract

In Staphylococcus aureus thioredoxin (Trx) it has been shown that mutation of the conserved active site tryptophan residue (Trp28) has a large effect on the protein stability, on the pKa of the nucleophilic cysteine and on the redox potential. Since these effects can either be due to the partially unfolding of the Trp28Ala mutant or to the absence of the indole side chain of Trp28 as possible interaction partner for the active site cysteines, the origin of the experimentally observed effects is not known and is beyond experimental approach. With theoretical pKa and density functional theory reactivity analysis on model systems where Trp28 has been replaced by an alanine within the structural environment of Trx it is shown that Trp28 does not affect the redox parameters of Trx. As such, the experimentally observed redox effects of the Trx W28A mutant might be due to structural changes induced by partial unfolding.

DOI10.1002/pro.269
Alternate JournalProtein Sci.
PubMed ID19902501
PubMed Central IDPMC2817855
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