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The conserved active site tryptophan of thioredoxin has no effect on its redox properties
Author(s) -
Roos Goedele,
Geerlings Paul,
Messens Joris
Publication year - 2010
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.269
Subject(s) - redox , chemistry , tryptophan , thioredoxin , cysteine , active site , ferredoxin thioredoxin reductase , indole test , alanine , mutant , protein structure , biophysics , stereochemistry , biochemistry , thioredoxin reductase , amino acid , enzyme , biology , inorganic chemistry , gene
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 With theoretical pKa and density functional theory reactivity analysis on model systems where Trp28 has been replaced by an alanine within the structural environment of Trx it is shown that Trp28 does not affect the redox parameters of Trx.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.