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dc.contributor.authorDutton, Rachel J.
dc.contributor.authorWayman, April
dc.contributor.authorWei, Jun-Rong
dc.contributor.authorRubin, Eric J.
dc.contributor.authorBeckwith, Jon
dc.contributor.authorBoyd, Dana
dc.date.accessioned2019-10-15T18:22:27Z
dc.date.issued2010
dc.identifier.citationDutton, R. J., A. Wayman, J.-R. Wei, E. J. Rubin, J. Beckwith, and D. Boyd. 2009. “Inhibition of Bacterial Disulfide Bond Formation by the Anticoagulant Warfarin.” Proceedings of the National Academy of Sciences 107 (1): 297–301. https://doi.org/10.1073/pnas.0912952107.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41552051*
dc.description.abstractBlood coagulation in humans requires the activity of vitamin K epoxide reductase (VKOR), the target of the anticoagulant warfarin (Coumadin). Bacterial homologs of VKOR were recently found to participate in a pathway leading to disulfide bond formation in secreted proteins of many bacteria. Here we show that the VKOR homolog from the bacterium Mycobacterium tuberculosis, the causative agent of human tuberculosis, is inhibited by warfarin and that warfarin-resistant mutations of mycobacterial VKOR appear in similar locations to mutations found in human patients who require higher doses of warfarin. Deletion of VKOR results in a severe growth defect in mycobacteria, and the growth of M. tuberculosis is inhibited by warfarin. The bacterial VKOR homolog may represent a target for antibiotics and a model for genetic studies of human VKOR. We present a simple assay in Escherichia coli, based on a disulfide-sensitive beta-galactosidase, which can be used to screen for stronger inhibitors of the M. tuberculosis VKOR homolog.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleInhibition of bacterial disulfide bond formation by the anticoagulant warfarin
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorRubin, Eric J.::2ccf3691d766f02c048797e00c06cc44::600
dc.date.available2019-10-15T18:22:27Z
dash.workflow.comments1Science Serial ID 90566
dc.identifier.doi10.1073/pnas.0912952107
dash.source.volume107;1
dash.source.page297


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