{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T09:44:07Z","timestamp":1756460647580,"version":"3.41.2"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MOE | Korea Environmental Industry and Technology Institute","award":["2021003380003"],"award-info":[{"award-number":["2021003380003"]}]},{"DOI":"10.13039\/501100002457","name":"Chosun University","doi-asserted-by":"crossref","award":["2017"],"award-info":[{"award-number":["2017"]}],"id":[{"id":"10.13039\/501100002457","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,1,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In pathogenic bacteria, the flavohemoglobin Hmp is crucial in metabolizing the cytotoxic levels of nitric oxide (NO) produced in phagocytic cells, contributing to bacterial virulence. Hmp expression is predominantly regulated by the Rrf2 family transcription repressor NsrR in an NO-dependent manner; however, the underlying molecular mechanism in enterobacteria remains poorly understood. In this study, we identified Val43 of\n            <jats:italic>Salmonella<\/jats:italic>\n            Typhimurium NsrR (StNsrR) as a critical amino acid residue for regulating Hmp expression. The Val43-to-Ala-substituted mutant NsrR isolated through random and site-directed mutagenesis showed high binding affinity to the target DNA irrespective of NO exposure, resulting in a severe reduction in\n            <jats:italic>hmp<\/jats:italic>\n            transcription and slow NO metabolism in\n            <jats:italic>Salmonella<\/jats:italic>\n            under NO-producing conditions. Conversely, the Val43-to-Glu-substituted NsrR caused effects similar to\n            <jats:italic>nsrR<\/jats:italic>\n            null mutation, which directed\n            <jats:italic>hmp<\/jats:italic>\n            transcription and NO metabolism in a constitutive way. Comparative analysis of the primary sequences of NsrR and another NO-sensing Rrf2 family regulator, IscR, from diverse bacteria, revealed that Val43 of enterobacterial NsrR corresponds to Ala in\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            or\n            <jats:italic>Streptomyces coelicolor<\/jats:italic>\n            NsrR and Glu in enterobacterial IscR, all of which are located in the DNA recognition helix \u03b13. The predicted structure of StNsrR in complex with the\n            <jats:italic>hmp<\/jats:italic>\n            DNA suggests dissimilar spatial stoichiometry in the interactions of Val43 and its substituted residues with the target DNA, consistent with the observed phenotypic changes in StNsrR Val43 mutants. Our findings highlight the discriminative roles of the NsrR recognition helix in regulating species-specific target gene expression, facilitating effective NO detoxification strategies in bacteria across diverse environments.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The precise regulation of flavohemoglobin Hmp expression by NsrR is critical for bacterial fitness, as excessive Hmp expression in the absence of NO can disturb bacterial redox homeostasis. While the molecular structure of\n              <jats:italic>Streptomyces coelicolor<\/jats:italic>\n              NsrR has been recently identified, the specific molecular structures of NsrR proteins in enterobacteria remain unknown. Our discovery of the crucial role of Val43 in the DNA recognition helix \u03b13 of\n              <jats:italic>Salmonella<\/jats:italic>\n              NsrR offers valuable insights into the Hmp modulation under NO stress. Furthermore, the observed amino acid polymorphisms in the \u03b13 helices of NsrR proteins across different bacterial species suggest the diverse evolution of NsrR structure and gene regulation in response to varying levels of NO pressure within their ecological niches.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.03024-23","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T14:02:22Z","timestamp":1701871342000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Val43 residue of NsrR is crucial for the nitric oxide response of\n            <i>Salmonella<\/i>\n            Typhimurium"],"prefix":"10.1128","volume":"12","author":[{"given":"Hee Jeong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Chosun University School of Dentistry , Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Won","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Chosun University School of Dentistry , Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Choa","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Chosun University School of Dentistry , Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi Rae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Chosun University School of Dentistry , Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hojung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Chonnam National University , Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eungseok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Chonnam National University , Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5284-9709","authenticated-orcid":true,"given":"Iel Soo","family":"Bang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Chosun University School of Dentistry , Gwangju, Republic of 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