@article{ref1,
title="The suicide substrate reaction between plasminogen activator inhibitor 1 and thrombin is regulated by the cofactors vitronectin and heparin",
journal="Blood",
year="1997",
author="van Meijer, M. and Smilde, A. and Tans, G. and Nesheim, M. E. and Pannekoek, H. and Horrevoets, A. J.",
volume="90",
number="5",
pages="1874-1882",
abstract="The interaction of thrombin with plasminogen activator inhibitor 1 (PAI-1) is shown to result in the simultaneous formation of both cleaved PAI-1 and a sodium dodecyl sulfate-stable thrombin-PAI-1 complex. The kinetics of this reaction can be described by a &quot;suicide substrate&quot; mechanism that includes a branched reaction pathway, which terminates in either the stable inhibitor-enzyme complex or the cleaved inhibitor plus free enzyme. Because of the branched pathway, approximately three moles of PAI-1 are needed to completely inhibit one mole of thrombin. Heparin and vitronectin enhance the rate of inhibition from 9.8 x 10(2) L mol(-1) s(-1) to 6.2 x 10(4) L mol(-1) s(-1) and 2.1 x 10(5) L mol(-1) s(-1), respectively, under optimal conditions. In addition to enhancing the rate of inhibition, both cofactors increase the apparent stoichiometry of the PAI-1-thrombin interaction, with cofactor concentration dependencies similar to the inhibition reaction. Thus, at 37 degrees C approximately six cleavage reactions occur per inhibition reaction. Therefore, thrombin will efficiently inactivate PAI-1 in the presence of either vitronectin or heparin, unless a sufficient excess of the inhibitor is present. These results show that physiological cofactors are able to switch a protease-serpin inhibition reaction to a substrate reaction, depending on the local concentrations of each of the components.<p /><p>Language: en</p>",
language="en",
issn="0006-4971",
doi="",
url="http://dx.doi.org/"
}