Structural and functional relations among thioredoxins of different species

Authors

  • Dr. Hans Eklund,

    Corresponding author
    1. Department of Molecular Biology, Swedish University of Agricultural Sciences, Biomedical Center, S-751 24 Uppsala, Sweden
    • Department of Molecular Biology, Swedish University of Agricultural Sciences, Biomedical Center, S-751 24 Uppsala, Sweden
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  • Florence K. Gleason,

    1. Department of Plant Biology, University of Minnesota, St. Paul, Minnesota 55108
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  • Arne Holmgren

    1. Department of Physiological Chemistry, Karolinska Institute, S-104 01 Stockholm, Sweden
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Abstract

Three-dimensional models have been constructed of homologous thioredoxins and protein disulfide isomerases based on the high resolution x-ray crystallographic structure of the oxidized form of Escherichia coli thioredoxin. The thioredoxins, from archebacteria to humans, have 27–69% sequence identity to E. coli thioredoxin. The models indicate that all the proteins have similar three-dimensional structures despite the large variation in amino acid sequences. As expected, residues in the active site region of thioredoxins are highly conserved. These include Asp-26, Ala-29, Trp-31, Cys-32, Gly-33, Pro-34, Cys-35, Asp-61, Pro-76, and Gly-92. Similar residues occur in most protein disulfide isomerase sequences. Most of these residues form the surface around the active site that appears to facilitate interactions with other enzymes.

Other structurally important residues are also conserved. A proline at position 40 causes a kink in the alpha-2 helix and thus provides the proper position of the active site residues at the amino end of this helix. Pro-76 is important in maintaining the native structure of the molecule. In addition, residues forming the internal contact surfaces between the secondary structural elements are generally unchanged such as Phe-12, Val-25, and Phe-27.

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