Allosteric regulation of the cofactor dependent serine protease coagulation factor VIIa

The integration of structure and function analysis of the tissue factor-fac tor VIIa complex has provided a detailed view of the functional surface of the extrinsic activation complex. An incomplete zymogen to enzyme transitio n is responsible for the strict cofactor dependence of catalytic function o f factor VIIa. The mutational analysis demonstrates that factor VIIa is all osterically regulated by specific conformational linkages that involve the cofactor binding site, the catalytic cleft, and the macromolecular substrat e exosite. Regions of the flexible activation domain appear to play an impo rtant role in the allosteric regulation of this cofactor-dependent coagulat ion serine protease. (Trends Cardiovasc Med 1998;8:350-356) (C) 1998, Elsev ier Science Inc.