Structural and Functional Insights into GGCX-FIX Interaction: Implications for Vitamin K-Dependent Bleeding Disorders.

Gamma-carboxylation, catalyzed by γ-glutamyl carboxylase (GGCX), is a critical post-translational modification essential for the biological activity of vitamin K-dependent proteins (VKDPs). Mutations in GGCX, depending on their specific location, result in vitamin K-dependent coagulation factor deficiency type 1 (VKCFD1), which encompasses a broad spectrum of clinical manifestations ranging from mild to severe, including bleeding disorders, osteoporosis, and vascular calcification. The limited knowledge of GGCX's structure and functional regions hinders our understanding of the consequences of GGCX mutations and the treatment for VKCFD1.