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

  • Roland J. Siezen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 379)


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.


Homology Modelling Substrate Binding Color Insert Leader Peptidase Enzyme Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Roland J. Siezen
    • 1
  1. 1.Department of Biophysical ChemistryNIZOEdeNetherlands

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