{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:49:21Z","timestamp":1790430561017,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,2]]},"abstract":"<jats:p>\n                    Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity. We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages. Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF\n                    <jats:italic>in vitro<\/jats:italic>\n                    with high affinity (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    = 27 nM). A crystal structure of EF-CaM-PMEApp reveals that the catalytic site of EF forms better van der Waals contacts and more hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the \u224810,000-fold higher affinity EF-CaM has for PMEApp versus ATP. Adefovir dipivoxil is a clinically approved drug that can block the action of an anthrax toxin. It can be used to address the role of EF in anthrax pathogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0306552101","type":"journal-article","created":{"date-parts":[[2004,3,2]],"date-time":"2004-03-02T21:33:11Z","timestamp":1078263191000},"page":"3242-3247","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":95,"title":["Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection"],"prefix":"10.1073","volume":"101","author":[{"given":"Yuequan","family":"Shen","sequence":"first","affiliation":[{"name":"Ben-May Institute for Cancer Research, Committee on Neurobiology, and Department of Pathology, University of Chicago, 924 East 57th Street, Chicago, IL 60637; andGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia L.","family":"Zhukovskaya","sequence":"additional","affiliation":[{"name":"Ben-May Institute for Cancer Research, Committee on Neurobiology, and Department of Pathology, University of Chicago, 924 East 57th Street, Chicago, IL 60637; 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