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The probable conformation of substrates recognized by dipeptidyl-peptidase IV and some aspects of the catalytic mechanism derived from theoretical investigations

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Summary

By theoretical conformational investigations of substrates and nonsubstrates of the enzyme dipeptidyl-peptidase IV (DP IV) as well as dipeptide-esters using the ECEPP83 method we determined the structure of peptides recognized and cleaved by the enzyme. From a comparison of all possible structures for the substrates with conformations not possible in nonsubstrates we concluded that a single conformation explains substrate specificities of DP IV. This conformation is characterized by the following dihedral angles: {ie159-1}, {ie159-2}, {ie159-3}, {ie159-4}, and {ie159-5}. The conclusions were supported by comparisons of molecular electrostatic potentials calculated with the molecular graphics program HAMOG.

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Authors and Affiliations

  1. Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Weinbergweg 16a, Halle/Saale, Germany

    W. Brandt, T. Lehmann, T. Hofmann & A. Barth

  2. Department of Chemistry, University of Kansas, 66045-0046, Lawrence, KS, U.S.A.

    R. L. Schowen

  3. Department of Biochemistry, University of Kansas, 66045-0046, Lawrence, KS, U.S.A.

    R. L. Schowen

Authors
  1. W. Brandt
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  2. T. Lehmann
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  3. T. Hofmann
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  4. R. L. Schowen
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  5. A. Barth
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Brandt, W., Lehmann, T., Hofmann, T. et al. The probable conformation of substrates recognized by dipeptidyl-peptidase IV and some aspects of the catalytic mechanism derived from theoretical investigations. J Computer-Aided Mol Des 6, 159–174 (1992). https://doi.org/10.1007/BF00129426

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  • DOI: https://doi.org/10.1007/BF00129426

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