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Slow thrombin is zymogen‐like
Author(s) -
HUNTINGTON J. A.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03365.x
Subject(s) - zymogen , thrombin , allosteric regulation , proteases , serine protease , chemistry , protease , biochemistry , enzyme , coagulation , biology , platelet , immunology , medicine , psychiatry
Summary. Blood coagulation is the result of a cascade of zymogen activation events; however, its initiation is allosteric. Factor VIIa circulates in a zymogen‐like state and is allosterically activated by binding to tissue factor. Thrombin, the final protease generated in the blood coagulation cascade, has also been shown to exist in a low activity state in the absence of cofactors, and the structural features of this ‘slow’ form have been studied for many years. In this manuscript, I will review the general features that render zymogens inactive and how proteolytic cleavage results in activation, but I will also show how this distinction is blurred by zymogens that have activity (protease‐like zymogens) and proteases with low activity (zymogen‐like proteases). This will then be applied in the analysis of slow thrombin to reveal how allosteric activation of thrombin simply reflects the conversion from a zymogen‐like enzyme to an active serine protease.