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Slow thrombin is zymogen-like.

ABSTRACT: 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.

SUBMITTER: Huntington JA

PROVIDER: S-EPMC2717038 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Slow thrombin is zymogen-like.

Huntington J A JA

Journal of thrombosis and haemostasis : JTH 20090701

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 gen ...[more]

PMID: 19630791

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