{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:46:49Z","timestamp":1788349609096,"version":"build-2803163510"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,12,13]]},"abstract":"<jats:p>\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    , the causative agent of anthrax, is a worldwide problem because of the need for effective treatment of respiratory infections shortly after exposure. One potential key enzyme of\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    to be targeted by antiproliferative drugs is ribonucleotide reductase. It provides deoxyribonucleotides for DNA synthesis needed for spore germination and growth of the pathogen. We have cloned, purified, and characterized the tyrosyl radical-carrying NrdF component of\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    class Ib ribonucleotide reductase. Its EPR spectrum points to a hitherto unknown three-dimensional geometry of the radical side chain with a 60\u00b0 rotational angle of C\n                    <jats:sub>\u03b1<\/jats:sub>\n                    -(C\n                    <jats:sub>\u03b2<\/jats:sub>\n                    -C\n                    <jats:sub>1<\/jats:sub>\n                    )-plane of the aromatic ring. The unusual relaxation behavior of the radical signal and its apparent lack of line broadening at room temperature suggest a weak interaction with the nearby diiron site and the presence of a water molecule plausibly bridging the phenolic oxygen of the radical to a ligand of the diiron site. We show that\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    cells are surprisingly resistant to the radical scavenger hydroxyurea in current use as an antiproliferative drug, even though its NrdF radical is efficiently scavenged\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Importantly, the antioxidants hydroxylamine and\n                    <jats:italic>N<\/jats:italic>\n                    -methyl hydroxylamine scavenge the radical several orders of magnitude faster and prevent\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    growth at several hundred-fold lower concentrations compared with hydroxyurea. Phylogenetically, the\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    NrdF protein clusters together with NrdFs from the pathogens\n                    <jats:italic>Bacillus cereus<\/jats:italic>\n                    ,\n                    <jats:italic>Bacillus thuringiensis<\/jats:italic>\n                    ,\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , and\n                    <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                    . We suggest the potential use of N-hydroxylamines in combination therapies against infections by\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    and closely related pathogens.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0506410102","type":"journal-article","created":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T20:25:23Z","timestamp":1133468723000},"page":"17946-17951","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["Efficient growth inhibition of\n                    <i>Bacillus anthracis<\/i>\n                    by knocking out the ribonucleotide reductase tyrosyl radical"],"prefix":"10.1073","volume":"102","author":[{"given":"Eduard","family":"Torrents","sequence":"first","affiliation":[{"name":"Departments of Molecular Biology and Functional Genomics and Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Sahlin","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biology and Functional Genomics and Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Biglino","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biology and Functional Genomics and Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Gr\u00e4slund","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biology and Functional Genomics and Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt-Marie","family":"Sj\u00f6berg","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biology and Functional Genomics and Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,12]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.55.1.647"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0810.020353"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.17.2236"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(01)00014-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-002-2311-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2001.2637"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01586"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26133-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002751200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(88)58067-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00221a030"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)43628-9"},{"key":"e_1_3_2_13_2","first-page":"156","volume":"82","year":"1989","unstructured":"Bernhard, W. 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