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Structural Modeling Insights into Human VKORC1 Phenotypes
Vitamin 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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555152/ https://www.ncbi.nlm.nih.gov/pubmed/26287237 http://dx.doi.org/10.3390/nu7085313 |
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author | Czogalla, Katrin J. Watzka, Matthias Oldenburg, Johannes |
author_facet | Czogalla, Katrin J. Watzka, Matthias Oldenburg, Johannes |
author_sort | Czogalla, Katrin J. |
collection | PubMed |
description | Vitamin 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. |
format | Online Article Text |
id | pubmed-4555152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-45551522015-09-01 Structural Modeling Insights into Human VKORC1 Phenotypes Czogalla, Katrin J. Watzka, Matthias Oldenburg, Johannes Nutrients Review Vitamin 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. MDPI 2015-08-14 /pmc/articles/PMC4555152/ /pubmed/26287237 http://dx.doi.org/10.3390/nu7085313 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Czogalla, Katrin J. Watzka, Matthias Oldenburg, Johannes Structural Modeling Insights into Human VKORC1 Phenotypes |
title | Structural Modeling Insights into Human VKORC1 Phenotypes |
title_full | Structural Modeling Insights into Human VKORC1 Phenotypes |
title_fullStr | Structural Modeling Insights into Human VKORC1 Phenotypes |
title_full_unstemmed | Structural Modeling Insights into Human VKORC1 Phenotypes |
title_short | Structural Modeling Insights into Human VKORC1 Phenotypes |
title_sort | structural modeling insights into human vkorc1 phenotypes |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555152/ https://www.ncbi.nlm.nih.gov/pubmed/26287237 http://dx.doi.org/10.3390/nu7085313 |
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