Warfarin has been the most widely prescribed anticoagulant for decades. It functions by inhibiting the membrane enzyme vitamin K epoxide reductase (VKOR), but the molecular details of this effect have remained elusive. Two new studies shed light on the warfarin-VKOR interaction. The work has implications for precision medicine and could guide drug discovery.
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References
Pirmohamed, M. Br. J. Clin. Pharmacol. 62, 509–511 (2006).
Pirmohamed, M., Kamali, F., Daly, A.K. & Wadelius, M. Trends Pharmacol. Sci. 36, 153–163 (2015).
Wysowski, D.K., Nourjah, P. & Swartz, L. Arch. Intern. Med. 167, 1414–1419 (2007).
Li, T. et al. Nature 427, 541–544 (2004).
Rost, S. et al. Nature 427, 537–541 (2004).
Shen, G. et al. Nat. Struct. Mol. Biol. 24, 69–76 (2016).10.1038/nsmb.3333
Czogalla, K.J. et al. Nat. Struct. Mol. Biol. 24, 77–85 (2017).
Presnell, S.R. & Stafford, D.W. Thromb. Haemost. 87, 937–946 (2002).
Booth, S.L. Annu. Rev. Nutr. 29, 89–110 (2009).
Dutton, R.J., Boyd, D., Berkmen, M. & Beckwith, J. Proc. Natl. Acad. Sci. USA 105, 11933–11938 (2008).
Dutton, R.J. et al. Proc. Natl. Acad. Sci. USA 107, 297–301 (2010).
Li, W. et al. Nature 463, 507–512 (2010).
Liu, S., Cheng, W., Fowle Grider, R., Shen, G. & Li, W. Nat. Commun. 5, 3110 (2014).10.1038/ncomms4110
Tie, J.K., Jin, D.Y. & Stafford, D.W. J. Biol. Chem. 287, 33945–33955 (2012).
Fasco, M.J., Principe, L.M., Walsh, W.A. & Friedman, P.A. Biochemistry 22, 5655–5660 (1983).
Kimmel, S.E. et al. N. Engl. J. Med. 369, 2283–2293 (2013).
Pirmohamed, M. et al. N. Engl. J. Med. 369, 2294–2303 (2013).
Drew, L. Nature 537, S60–S62 (2016).
Relling, M.V. & Evans, W.E. Nature 526, 343–350 (2015).
Kroncke, B.M., Vanoye, C.G., Meiler, J., George, A.L. Jr. & Sanders, C.R. Biochemistry 54, 2551–2559 (2015).
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Hilton, J., Van Horn, W. New pieces to an old puzzle: identifying the warfarin-binding site that prevents clotting. Nat Struct Mol Biol 24, 5–6 (2017). https://doi.org/10.1038/nsmb.3356
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DOI: https://doi.org/10.1038/nsmb.3356