Vitamin k-dependent polypeptides such as protein C where substitution at amino acid sites 11, 12, 29, 33 or 34 affects membrane binding affinity of the protein and ultimately blood clotting ability

摘要

A vitamin K-dependent polypeptide comprises a modified GLA domain that comprises a least one amino acid substitution at residues 11,12,29, or 34. The modified GLA domain enhances membrane binding affinity. The polypeptide may further include an amino acid substitution at amino acid 33. The isolated nucleic acid encoding the polypeptide is also described. A protein C or activated protein C can comprise a modified GKA domain. Also described is a pharmaceutical composition comprising a polypeptide with the modified GLA domain, whereby it is suitable for use to modulate clot formation in a mammal.