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Subtilisin Enzymes pp 63–73Cite as

Modelling and Engineering of Enzyme/Substrate Interactions in Subtilisin-Like Enzymes of Unknown 3-Dimensional Structure

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 379))

Abstract

Homology modelling was used to predict enzyme-substrate interactions in three entirely different subtilisin-like enzymes of unknown three-dimensional structure, i.e. (a) cell-envelope proteinase of Lactococcus lactis, (b) putative leader peptidase for pre-nisin from L. lactis, and (c) human furin. Models were based on known three-dimensional structures of subtilisins and thermitase in complex with inhibitors. Detailed analysis of interactions of the P1-P4 residues of model substrates with the S1-S4 binding sites in each enzyme suggest that electrostatic interactions at all four binding sites can contribute to binding and hence to specificity. In particular, one or more negative charges in the SI or S4 pockets can lead to a high selectivity for Arg residues in the substrate.

Many of the predicted interactions have been confirmed by engineering of either enzyme, substrate of both.

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Authors and Affiliations

  1. Department of Biophysical Chemistry, NIZO, P.O.Box 20, 671OBA , Ede, Netherlands

    Roland J. Siezen

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  1. Roland J. Siezen
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Editors and Affiliations

  1. Genecor International, Inc., South San Francisco, California, USA

    Richard Bott

  2. European Molecular Biology Laboratory, Hamburg, Germany

    Christian Betzel

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© 1996 Plenum Press, New York

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Siezen, R.J. (1996). Modelling and Engineering of Enzyme/Substrate Interactions in Subtilisin-Like Enzymes of Unknown 3-Dimensional Structure. In: Bott, R., Betzel, C. (eds) Subtilisin Enzymes. Advances in Experimental Medicine and Biology, vol 379. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0319-0_8

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  • DOI: https://doi.org/10.1007/978-1-4613-0319-0_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-45108-9

  • Online ISBN: 978-1-4613-0319-0

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