Title: Homology Modeling of The Catalytic Domain of Human Furin - A Model For The Eukaryotic Subtilisin-Like Proprotein Convertases
Authors: Siezen, Rj
Creemers, John
Van de Ven, Willem #
Issue Date: 1994
Series Title: European Journal of Biochemistry vol:222 issue:2 pages:255-266
Abstract: A model is presented for the three-dimensional structure of the catalytic domain of the human serine proteinase furin and its interaction with model substrates. This homology model is based on the crystal structures of subtilisin BPN' and thermitase in complex with the inhibitor eglin, and it also applies to other members of the eukaryotic subtilisin-like proprotein convertases. Predictions are made of the general protein fold, inserted loops, disulfide bonds, Ca2+-binding sites and salt bridges. A detailed prediction of the substrate-binding region attempts to explain the basis of speci ficity for multiple basic residues preceding the cleavage site. Specific acidic residues in the S1, S2 and S4 subsites of the substrate-binding region of furin are identified which appear to be of particular importance, while residues of the S2', S3, S5 and S6 subsites may also contribute to substrate binding. Based on this model, protein engineering can be employed not only to test the predicted enzyme-substrate interactions, as demonstrated for human furin, but, equally importantly, to design proprotein convertases with a desired specificity, or to design novel substrates or inhibitors.
ISSN: 0014-2956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
# (joint) last author

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