Mechanisms of Macromolecular Protease Inhibitors

Graduate Group in Biophysics, University of California-San Francisco, San Francisco, CA 94143-2240, USA.
ChemBioChem (Impact Factor: 3.09). 11/2010; 11(17):2341-6. DOI: 10.1002/cbic.201000442
Source: PubMed


Relatively few design principles underlie the inhibition mechanisms of macromolecular protease inhibitors. These inhibitors tend to compete with substrate binding either through direct competition or deformation of the protease active site; they gain potency and specificity by burying a large surface area and through contacts with specific exosites. Protein engineering has allowed both potency and specificity to be modified.

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Available from: Charles S Craik, Oct 08, 2015
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    • "Considering eleven mammalian species (Figure 3), methionine is always present at this position except in mouse. Moreover methionine in this position (P1 position of RCL region) has been demonstrated to be involved in the interaction of AAT with its substrates, the proteases [26,27]. Different phylogeny studies of the serpin superfamily showed the importance of the amino acid composition of the RCL region to determine the ability to bind protease and non protease ligand [1,28]. "
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