{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:12:14Z","timestamp":1789650734257,"version":"4.0.0"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100012538","name":"Swedish Cancer Foundation","doi-asserted-by":"publisher","award":["20 1210 PjF"],"award-info":[{"award-number":["20 1210 PjF"]}],"id":[{"id":"10.13039\/100012538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014437","name":"Wenner-Gren Stiftelserna","doi-asserted-by":"publisher","award":["personal grant"],"award-info":[{"award-number":["personal grant"]}],"id":[{"id":"10.13039\/100014437","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Academic Infrastructure for Supercomputing in Sweden","award":["2025\/22-619"],"award-info":[{"award-number":["2025\/22-619"]}]},{"DOI":"10.13039\/501100002805","name":"Carl Tryggers Stiftelse f\u00f6r Vetenskaplig Forskning","doi-asserted-by":"publisher","award":["CTS 20:361"],"award-info":[{"award-number":["CTS 20:361"]}],"id":[{"id":"10.13039\/501100002805","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2019-01400"],"award-info":[{"award-number":["2019-01400"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The prevalent transcriptional repressor NrdR binds to highly conserved sequences in the promoter regions of prokaryotic operons encoding the essential enzyme ribonucleotide reductase. The NrdR-binding sites consist of two partially palindromic 16 bp sequences (NrdR boxes) separated by a 15\u201316 bp linker sequence. We have assessed the requirement of both boxes for binding, the propensity of different NrdRs to bind to heterologous binding sites, and that the linker sequence is only limited to length and not sequence conservation. As we have observed several deviations from the conserved sequences of the NrdR boxes, we have tested the conservation requirements of individual base pairs in the NrdR boxes using a synthetic DNA fragment (Synt DNA) to which the NrdR proteins from the actinomycete\n                      <jats:italic toggle=\"yes\">Streptomyces coelicolor<\/jats:italic>\n                      and the gammaproteobacterium\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      bind equally well as to their homologous binding sites. By introducing isolated mutations to Synt DNA and testing the binding capacity of NrdR from\n                      <jats:italic toggle=\"yes\">S. coelicolor<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      , we expand our understanding of what criteria are needed to build a functional binding site for the NrdR repressor. Our results enable more precise identification of NrdR-binding sites across bacterial genomes, which can be used to explore NrdR and its regulons as potential targets for the development of novel antimicrobials.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The transcriptional repressor NrdR is strictly prokaryotic, occurring in 77% of bacterial genomes, and 22% of archaeal genomes. It binds to highly conserved sequences in the promoter regions of the genes encoding the essential enzyme ribonucleotide reductase that provides cells with\n                        <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                        building blocks for DNA synthesis. Repression of ribonucleotide reductase expression leads to a lack of replication and cell proliferation. In this report, we have characterized in detail the generality of the partially palindromic sequences constituting the NrdR-binding site. As NrdR controls the sole\n                        <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                        pathways for production of DNA building blocks in bacteria and not in eukaryotes, our results will facilitate screens for novel antimicrobials utilizing the NrdR protein and its homologous regulons in pathogenic bacteria.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00274-26","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:21:57Z","timestamp":1787840517000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Ribonucleotide reductase repression: a mutational study of NrdR-binding motifs"],"prefix":"10.1128","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4107-8069","authenticated-orcid":false,"given":"Saher","family":"Shahid","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f0yaq80","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Biophysics, Stockholm University","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8779-6464","authenticated-orcid":true,"given":"Daniel","family":"Lundin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f0yaq80","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Biophysics, Stockholm University","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3094-1998","authenticated-orcid":false,"given":"Inna","family":"Rozman 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