Structure-function relationships in human ?- and ?-thrombins

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Abstract
Human pro-coagulant α-thrombin may be proteolyzed under controlled conditions to the non-coagulant β- and γ-thrombin forms. These derivative forms nonetheless retain esterase and amidase activities with small substrates as well as several other thrombin functions. Structurally, human γ-thrombin consists of three non-covalently associated fragments which retain structural integrity as measured by several spectroscopic criteria as well as enzymatic function. The protein folding characteristics of three-chain γ-thrombin indicate that each fragment (domain) contains sufficient information to result in a correct renaturation of protein conformation. Those subtle structural differences which distinguish γ- from α-thrombin are most likely the obstructions to fibrinogen binding which account for the loss of clotting activity.