PPACK-thrombin is a noncompetitive inhibitor of alpha-thrombin binding to human platelets.
Recent studies from our laboratory indicate that purified kininogens are noncompetitive inhibitors of human alpha-thrombin but not PPACK-thrombin, binding to human washed platelets. In order to understand the mechanism by which the kininogens inhibit alpha-thrombin binding, investigations were initiated to determine if alpha-thrombin and PPACK-thrombin bound to the same site on human platelets. Initial investigations reveal that alpha-thrombin is a more potent inhibitor of 125I-PPACK-thrombin binding than PPACK-thrombin. Further studies show that PPACK-thrombin is a noncompetitive inhibitor of 125I-alpha-thrombin binding to platelets. These studies suggest that human alpha-thrombin binds on the platelet surface to a different site or binds differently to the same site from PPACK-thrombin. These data indicate that the ability of the kininogens to block alpha-thrombin binding to platelets but not PPACK-thrombin binding results from these thrombins having either two different binding sites or one binding site on the platelet surface which they interact with differently.
Schmaier
A H
AH
University of Michigan, Ann Arbor 48109.
Meloni
F J
FJ
Nawarawong
W
W
Jiang
Y P
YP
D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism*; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D013917:Thrombin; C050815:phenylalanyl-prolyl-arginine chloromethyl ketone-thrombin