{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:26:38Z","timestamp":1791267998533,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2015,8,14]],"date-time":"2015-08-14T00:00:00Z","timestamp":1439510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BONFOR","award":["2014-1-3"],"award-info":[{"award-number":["2014-1-3"]}]},{"DOI":"10.13039\/100004875","name":"DFG","doi-asserted-by":"publisher","award":["Ol 100 5-1"],"award-info":[{"award-number":["Ol 100 5-1"]}],"id":[{"id":"10.13039\/100004875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004702","name":"Baxter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain \u03b3-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.<\/jats:p>","DOI":"10.3390\/nu7085313","type":"journal-article","created":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T02:36:16Z","timestamp":1439865376000},"page":"6837-6851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Structural Modeling Insights into Human VKORC1 Phenotypes"],"prefix":"10.3390","volume":"7","author":[{"given":"Katrin","family":"Czogalla","sequence":"first","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn,  Bonn 53105, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Watzka","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn,  Bonn 53105, Germany"},{"name":"Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn 53127, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn,  Bonn 53105, Germany"},{"name":"Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn 53127, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10540","DOI":"10.1074\/jbc.M413982200","article-title":"Engineering of a recombinant vitamin K-dependent gamma-carboxylation system with enhanced gamma-carboxyglutamic acid forming capacity: Evidence for a functional CXXC redox center in the system","volume":"280","author":"Wajih","year":"2005","journal-title":"J. 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