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Inhibition of bacterial disulfide bond formation by the anticoagulant warfarin
Dutton RJ, Wayman A, Wei JR, Rubin EJ, Beckwith J, Boyd D.
Reviewers: David S. Palilla, MD and Theodore A. Alston, MD, PhD
Four strains of warfarin-resistant microbes were isolated with the aid of mutagenic chemicals. Interestingly, the four mutations corresponded to genetic variations of VKOR found in warfarin-resistant humans. Further study of the enzyme from TB bacilli will be facilitated by its functional cloning into nonpathogenic E. coli. The authors have accomplished the transfer, which is expected to facilitate the screening for warfarin analogs for improved activity as anticoagulants and/or antibiotics. In allied work toward that goal, the three-dimensional structure of the bacterial VKOR has been elucidated this year (Li W et al, Nature 2010 Jan 28;463:507-12).
Though humans and bacteria both seem to require enzymatic reduction of vitamin K, bacteria are not known to carboxylate any of their proteins. Instead, vitamin K is involved in disulfide bond formation in bacterial proteins. It would be interesting to learn if this function of vitamin K was also exhibited in humans as further studies examining this effect of warfarin are undertaken. Regardless, potential uses of warfarin in the future will include more than anticoagulation and rat extermination.
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