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Structure-function relationships of mitochondrial monoamine oxidase A and B: chimaeric enzymes and site-directed mutagenesis studies

  • Conference paper
MAO — The Mother of all Amine Oxidases

Part of the book series: Journal of Neural Transmission. Supplement ((NEURAL SUPPL,volume 52))

Summary

To gain insight into the structure of monoamine oxidases (MAO) A and B, we investigated the properties of various chimaeric enzymes, engineered by moving progressively the junction between the NH2- and the COOH-termini of each MAO form. Whereas exchange of the ADP-binding sequence did not modify the catalytic properties of either MAO isoforms, chimaeras with increasing length of the NH2-terminus of MAO-A (up to position 256) showed a marked decrease in affinity towards substrates and inhibitors. Two sequences, spanning position 62 to 103 and 146 to 220, appeared of particular importance in putatively constituting the binding site of MAO-B. Conversely, the catalytic properties and specificity of MAO-A were insensitive to substitution of both the NH2- (up to position 112) and COOHtermini (from residue 395), but further modification of the central sequence of MAO-A was not compatible with activity. None of the engineered chimaeras showed a shift in substrate and inhibitor specificity. Investigation on MAO-B by site-directed mutagenesis revealed that His382 and Thr158 may represent residues relevant for MAO-B catalytic mechanism.

Mosé Da Prada died on April 25, 1995

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Authors and Affiliations

  1. Pharma Division, Preclinical Research, Nervous System Diseases, F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Dr. A. M. Cesura, J. Gottowik, G. Lang, P. Malherbe & M. Da Prada

  2. Pharma Division, Preclinical Research (PRPN, 70/304), F. Hoffmann-La Roche Ltd, CH-4070, Basel, Switzerland

    Dr. A. M. Cesura

Authors
  1. Dr. A. M. Cesura
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  2. J. Gottowik
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  3. G. Lang
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  4. P. Malherbe
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  5. M. Da Prada
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Editor information

Editors and Affiliations

  1. Department of Pharmacology, The Bruce Rappaport Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel

    J. P. M. Finberg  & M. B. H. Youdim  & 

  2. Clinical Neurochemistry, Department of Psychiatry, University of Würzburg, Federal Republic of Germany

    P. Riederer

  3. Biochemistry Department, Trinity College, Dublin, Ireland

    K. F. Tipton

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© 1998 Springer-Verlag Wien

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Cesura, A.M., Gottowik, J., Lang, G., Malherbe, P., Da Prada, M. (1998). Structure-function relationships of mitochondrial monoamine oxidase A and B: chimaeric enzymes and site-directed mutagenesis studies. In: Finberg, J.P.M., Youdim, M.B.H., Riederer, P., Tipton, K.F. (eds) MAO — The Mother of all Amine Oxidases. Journal of Neural Transmission. Supplement, vol 52. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6499-0_18

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  • DOI: https://doi.org/10.1007/978-3-7091-6499-0_18

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83037-6

  • Online ISBN: 978-3-7091-6499-0

  • eBook Packages: Springer Book Archive

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