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A molecular model of the serine protease domain of activated protein C: application to the study of missense mutations causing protein C deficiency
Author(s) -
Wacey A. I.,
Pemberton S.,
Cooper D. N.,
Kakkar V. V.,
Tuddenham E. G. D.
Publication year - 1993
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1993.tb03067.x
Subject(s) - missense mutation , serine protease , mutation , protease , serine , genetics , chemistry , medicine , biology , biochemistry , gene , enzyme , phosphorylation
Summary. A molecular model of the serine protease domain of protein C was constructed by standard comparative methods. Individual missense mutations were inserted into the model and plausible explanations for their interference with protein C structure/function were derived through consideration of location, steric effects and protein stability. A hydrophilic cluster of many Arg and Lys residues, found adjacent to the active site cleft, is proposed to be involved in thrombomodulin and/or protein S interactions. Analysis of comparative binding studies also suggested the presence of an extended substrate binding pocket in the model.