Model of TAFIa inactivation. In zymogen TAFI, the dynamic flap (orange) is stabilized by the activation peptide (blue), which also hinders substrate access to the active site. Cleavage by thrombin releases the activation peptide, the substrate can enter, and mobility in the dynamic flap is increased. In time an irreversible conformational change occurs in the dynamic flap. The catalytic site is disrupted and the cryptic thrombin cleavage site at Arg302 (indicated by x) becomes accessible.