| Structural and functional characterization of tissue factor pathway inhibitor following degradation by matrix metalloproteinase 8 . ^^^ We have investigated the effect of MMP 8 degradation on the anticoagulant function of tissue factor pathway inhibitor ( TFPI ) as a potential pathological mechanism contributing to coagulation disorders . ^^^ MMP 8 cleaves TFPI following Ser ( 174 ) within the connecting region between the second and third Kunitz domains ( k ( cat ) / K ( m ) approximately 75 M ( 1 ) . s ( 1 ) ) as well as following Lys ( 20 ) within the NH ( 2 ) terminal region . ^^^ MMP 8 cleavage of TFPI decreases the anticoagulant activity of TFPI in factor Xa initiated clotting assays as well as the ability of TFPI to inhibit factor Xa in amidolytic assays . ^^^ Yet , MMP 8 cleavage does not alter the ability of TFPI to inhibit trypsin . ^^^ |