Slow thrombin is zymogen-like.
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.
Huntington
J A
JA
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. jah52@cam.ac.uk
D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*
D004792:Enzyme Precursors; D010447:Peptide Hydrolases; D013917:Thrombin