It is proposed to investigate and compare the structural basis for the specific proteolytic activity of Clr and Cls, serine proteases associated with the first component of complement, plasmin and thrombin. A two fold experimental approach will be used. First, the quantitative structure activity relationship of all four enzymes will be determined with respect to competititve inhibition by a series of mono and disubstituted benzamidines. The variation in the magnitude of the inhibition constant will be correlated by means of a computerized multiregression analysis with substituent constants which describe basic properties such as hydrophobicity, polarizability and charge. Second, functionally different exo affinity labeling reagents will be used to map the active sites of the enzymes. This will be accomplished by sequencing the portion of the polypeptide chain to which the labels are attached. The results of these experiments should provide insight to how serine proteases in the complement, clotting and fibrinolytic systems can exhibit narrow protein substrate and inhibitor specificity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK034028-03
Application #
3232413
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1983-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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