(The figure was prepared using the program MOLMOL (Koradi et al., 1996))
|
| The multi-domain Kazal-type thrombin inhibitor dipetalin (Dip) is expressed as fusion protein with the
plasminogen-activator staphylokinase. The fusion protein shows unaltered plasminogen-activating and
thrombin-inhibiting activities when compared to the single domains. Although in the first project period the key role
of domain Dip-I for the interaction with thrombin and trypsin was revealed, contributions of other molecular regions
remain to be clarified. The project aims especially at the determination of the contribution of domain Dip-II and the
interdomain linker between Dip-I and Dip-II with respect to functional and structural aspects. Further information
on the enzyme:inhibitor orientation is expected from mutations in the N-terminal binding loop. On the basis of the
determined structure-function relationship one will be able to tackle a functional optimization of dipetalin as well as
to evaluate the potential for a medical application. (The figure was prepared using the program MOLMOL (Koradi et al., 1996)) |
Related publications:
C. Icke, B. Schlott, O. Ohlenschläger, M. Hartmann,
K. Gührs and E. Glusa.
"Fusion proteins with anticoagulant and fibrinolytic properties: functional
studies and structural considerations"
Molecular Pharmacology 62 (2002), 203-209.
[Abstract]
[PDF file]
B. Schlott, J. Wöhnert, C. Icke, M. Hartmann,
R. Ramachandran, K. Gührs, E. Glusa, J. Flemming,
M. Görlach, F. Große and O. Ohlenschläger.
"Interaction of Kazal-type inhibitor domains with serine proteinases:
Biochemical and structural studies"
Journal of Molecular Biology 318 (2002), 533-546.
[Abstract]