Structural Modeling Insights into Human VKORC1 Phenotypes
AbstractVitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain γ-carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention and therapy of thromboembolism. Patients with these mutations require greater doses of VKA for stable anticoagulation than patients without mutations. The second phenotype, a very rare autosomal-recessive bleeding disorder caused by combined deficiency of vitamin K dependent clotting factors type 2 (VKCFD2) arises from a homozygous Arg98Trp mutation. The bleeding phenotype can be corrected by vitamin K administration. Here, we summarize published experimental data and in silico modeling results in order to rationalize the mechanisms of VKA resistance and VKCFD2. View Full-Text
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Czogalla, K.J.; Watzka, M.; Oldenburg, J. Structural Modeling Insights into Human VKORC1 Phenotypes. Nutrients 2015, 7, 6837-6851.
Czogalla KJ, Watzka M, Oldenburg J. Structural Modeling Insights into Human VKORC1 Phenotypes. Nutrients. 2015; 7(8):6837-6851.Chicago/Turabian Style
Czogalla, Katrin J.; Watzka, Matthias; Oldenburg, Johannes. 2015. "Structural Modeling Insights into Human VKORC1 Phenotypes." Nutrients 7, no. 8: 6837-6851.