Abstract
We studied the factors affecting the selectivity of peptidomimetic inhibitors of the highly homologous proteases matriptase and matriptase-2 across subpockets using docking simulations. We observed that the farther away a subpocket is located from the catalytic site, the more pronounced its role in selectivity. As a result of our exhaustive virtual screening, we biochemically validated novel potent and selective inhibitors of both enzymes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Catalytic Domain
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Humans
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Membrane Proteins / antagonists & inhibitors*
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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Molecular Docking Simulation
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Protein Structure, Tertiary
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Serine Endopeptidases / chemistry
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Serine Endopeptidases / metabolism*
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Serine Proteinase Inhibitors / metabolism*
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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Membrane Proteins
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Serine Proteinase Inhibitors
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Serine Endopeptidases
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matriptase
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matriptase 2