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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3811-3815. Prepublished online as a Blood First Edition Paper on August 4, 2005; DOI 10.1182/blood-2005-06-2495. This Article Full Text (PDF) All Versions of this Article: 2005-06-2495v1 106/12/3811    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sun, Y.-M. Articles by Stafford, D. W Search for Related Content PubMed PubMed Citation Articles by Sun, Y.-M. Articles by Stafford, D. W Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 23, 2005 Accepted July 28, 2005 Vitamin K epoxide reductase significantly improves carboxylation in a cell line over-expressing factor X Yan-Mei Sun, Da-Yun Jin, Rodney M Camire, and Darrel W Stafford* Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA * Corresponding author; email: dws{at}email.unc.edu. Previously we reported that we could increase the fraction of carboxylated factor X by reducing the affinity of the propeptide for its binding site on human gamma glutamyl carboxylase. We attributed this to an increased turnover rate. However, even with the reduced affinity propeptide, when sufficient over-production of factor X is achieved, there is still a significant fraction of uncarboxylated recombinant factor X. We report here that the factor X of such a cell line was only 52% carboxylated but that the fraction of carboxylated factor X could be increased to 92% by co-expressing the recently identified gene for vitamin K epoxide reductase. Because vitamin K is in excess in both the un-transfected and VKOR transfected cells, the simplest explanation for this result is that vitamin K epoxide reductase catalyzes both the reduction of vitamin K epoxide to vitamin K and the conversion of vitamin K to vitamin K hydroquinone. In addition to its mechanistic relevance, this observation has practical implications for over-producing recombinant vitamin K dependent proteins for therapeutic use. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: VKORC1: the little big protein Johannes Oldenburg Blood 2005 106: 3683-3684. [Full Text] [PDF] This article has been cited by other articles: N. Wajih, S. M. Hutson, and R. Wallin siRNA silencing of calumenin enhances functional factor IX production Blood, December 1, 2006; 108(12): 3757 - 3760. [Abstract] [Full Text] [PDF] D. Darghouth, K. W. Hallgren, R. L. Shtofman, A. Mrad, Y. Gharbi, A. Maherzi, R. Kastally, S. LeRicousse, K. L. Berkner, and J.-P. Rosa Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency Blood, September 15, 2006; 108(6): 1925 - 1931. [Abstract] [Full Text] [PDF]

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