[Inhibition of enzymatic activity of alpha-thrombin by low molecular weight synthetic inhibitor].
The effect of the organophosphoric inhibitor, SA-152, on the fibrinogen-coagulating and TAME-esterase activity of bovine alpha-thrombin was studied. The irreversible inhibition constants (k11 = 1.1 x 10(4) M-1.min-1,Ki = 0.7 x 10(-4) M, k2 = 0.8 min-1 towards the coagulating activity and kII = 0.7 x 10(4) M-1.min-1, Ki = 0.3 x 10(-4) M, k2 = 0.2 min-1 towards the esterase activity) were determined. The SA-152 inactivated alpha-thrombin was dialyzed and incubated with 0.5 M and 2.5 M NaCl and 10 mM TAME. There was no reconstitution of activity of the SA-152 modified alpha-thrombin after dialysis and treatment with high concentrations of NaCl and TAME. Heparin interactions with the anion-binding site of the high molecular weight recognition center in the alpha-thrombin molecule did not significantly influence the values of the kinetic constants for the enzyme inhibition by SA-152. This finding is consistent with the hypothesis on the irreversible binding of SA-152 in the active center of the enzyme.
Kireeva
E G
EG
Strukova
S M
SM
Dugina
T N
TN
Sokolov
V B
VB
Aksinenko
A Iu
AIu
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D005340:Fibrinogen / Q000037:antagonists & inhibitors; D007700:Kinetics; D008970:Molecular Weight; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D009943:Organophosphorus Compounds; C076860:SA 152; D005340:Fibrinogen; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D013917:Thrombin