A molecular model of the serine protease domain of activated protein C: application to the study of missense mutations causing protein C deficiency.
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.
Charter Molecular Genetics Laboratory, Thrombosis Research Institute, London.
A I
AI
Wacey
S
S
Pemberton
D N
DN
Cooper
V V
VV
Kakkar
E G
EG
Tuddenham
D000595:Amino Acid Sequence; D004789:Enzyme Activation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011486:Protein C / Q000737:chemistry* / Q000235:genetics; D020151:Protein C Deficiency; D012697:Serine Endopeptidases / Q000737:chemistry*
D011486:Protein C; D012697:Serine Endopeptidases