Two missense mutations identified in venous thrombosis patients impair the inhibitory function of the protein Z dependent protease inhibitor
Laura K Young, Nigel P Birch, Peter J Browett, Paul B Coughlin, Anita J Horvath, Neil S Van de Water, Paul A Ockelford, Paul L Harper
THROMBOSIS AND HAEMOSTASIS | GEORG THIEME VERLAG KG | Published : 2012
Protein Z-dependent protease inhibitor (ZPI) is a plasma inhibitor of factor (F)Xa and FXIa. In an earlier study, five mutations were identified within the ZPI gene of venous thrombosis patients and healthy controls. Two of these were nonsense mutations and three were missense mutations in important regions of the protein. Here we report that two of these latter three mutations, F145L and Q384R, impair the inhibitory function of ZPI in vitro. Recombinant wild-type and mutant proteins were prepared; stability in response to thermal challenge was similar. Inhibition of FXa in the presence of the cofactor protein Z was reduced 68-fold by the Q384R mutant; inhibition of FXIa by the F145L mutant ..View full abstract
This study was supported by a grant from the Auckland Medical Research Foundation.