Structural relationship between the hexameric and tetrameric family of glutamate dehydrogenases

Authors

  • K. Linda BRITTON,

    1. The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, England
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  • Patrick J. BAKER,

    1. The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, England
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  • David W. RICE,

    Corresponding author
    1. The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, England
      Correspondence to D. W. Rice, The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, England, S10 2TN
      Fax: +44742728697.
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  • Timothy J. STILLMAN

    1. The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, England
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Correspondence to D. W. Rice, The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, England, S10 2TN
Fax: +44742728697.

Abstract

The family of glutamate dehydrogenases include a group of hexameric oligomers with a subunit Mr of around 50000, which are closely related in amino acid sequence and a smaller group of tetrameric oligomers based on a much larger subunit with Mr 115000. Sequence comparisons have indicated a low level of similarity between the C-terminal portion of the tetrameric enzymes and a substantial region of the polypeptide chain for the more widespread hexameric glutamate dehydrogenases. In the light of the solution of the three dimensional structure of the hexameric NAD+-linked glutamate dehydrogenase from Clostridium symbiosum, we have undertaken a detailed examination of the alignment of the sequence for the C-terminal domain of the tetrameric Neurospora crassa glutamate dehydrogenase against the sequence and the molecular structure of that from C. symbiosum. This analysis reveals that the residues conserved between these two families are clustered in the three-dimensional structure and points to a remarkably similar layout of the glutamate-binding site and the active-site pocket, though with some differences in the mode of recognition of the nucleotide cofactor.

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