Structural studies of the interactions of normal and abnormal human plasmins with bovine basic pancreatic trypsin inhibitor.
Catalytic activity of human plasmin is inhibited by bovine basic pancreatic trypsin inhibitor (BPTI, also known as aprotinin). In spite of increased interest in the function of BPTI as an inhibitor of plasmin, the 3-D structure of the plasmin-BPTI complex has not yet been determined. Therefore, in the present paper, the structure of the plasmin-BPTI complex was constructed by the homology modeling method, which provided information about the high affinity of plasmin for BPTI. Moreover, normal mode analyses of free plasmin, free BPTI and the plasmin-BPTI complex were carried out to investigate the changes in dynamics following complex formation. After study of the plasmin-BPTI interaction, we also investigated the binding of BPTI with abnormal plasmin, theoretically and experimentally. The result showing that BPTI binds to abnormal plasmin in the same way as it does to normal plasmin supports the previous finding that the difference between normal and abnormal plasmins is very small and that the abnormality is localized to the catalytic site.
Takeda-Shitaka
M
M
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Kamiya
K
K
Miyata
T
T
Ohkura
N
N
Madoiwa
S
S
Sakata
Y
Y
Umeyama
H
H
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000737:chemistry*; D002417:Cattle; D005341:Fibrinolysin / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D020349:Surface Plasmon Resonance
D007611:Aprotinin; D005341:Fibrinolysin