{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:55:10Z","timestamp":1791194110543,"version":"4.1.0"},"reference-count":100,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New Zealand Royal Society Marsden Fund","award":["UOC1506"],"award-info":[{"award-number":["UOC1506"]}]},{"name":"Ministry of Business, Innovation and Employment Smart Ideas","award":["UOCX1706"],"award-info":[{"award-number":["UOCX1706"]}],"id":[{"id":"https:\/\/ror.org\/02jtq1b51","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019601","name":"Biomolecular Interaction Centre","doi-asserted-by":"publisher","award":["2034044"],"award-info":[{"award-number":["2034044"]}],"id":[{"id":"10.13039\/100019601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001530","name":"Canterbury Medical Research Foundation","doi-asserted-by":"publisher","award":["2034044"],"award-info":[{"award-number":["2034044"]}],"id":[{"id":"10.13039\/501100001530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018883","name":"Maurice Wilkins Centre","doi-asserted-by":"publisher","award":["2034044"],"award-info":[{"award-number":["2034044"]}],"id":[{"id":"10.13039\/501100018883","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council of Australia","award":["2034044"],"award-info":[{"award-number":["2034044"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01GM120600"],"award-info":[{"award-number":["1R01GM120600"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada Research Chairs program","award":["C150-2017-00015"],"award-info":[{"award-number":["C150-2017-00015"]}],"id":[{"id":"https:\/\/ror.org\/0517h6h17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Canadian Natural Science and Engineering Research Council Discovery","award":["DG-RGPIN-2019-05637"],"award-info":[{"award-number":["DG-RGPIN-2019-05637"]}]},{"name":"Canada Foundation","award":["CFI-37589"],"award-info":[{"award-number":["CFI-37589"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In Streptococcus pneumoniae, the RpiR transcriptional regulator NanR (SpNanR) senses sialic acid in the environment and upregulates transcription of the nan and sia A operons to increase uptake and metabolism of sialic acid. The molecular basis of this activation is unknown. Here, we demonstrate that SpNanR binds N-acetylmannosamine-6-phosphate, a metabolite of sialic acid catabolism. SpNanR exists in a dimer\u2013tetramer equilibrium, and N-acetylmannosamine-6-phosphate binding strongly stabilizes the tetramer. Crystal structures and site-specific substitutions demonstrate that N-acetylmannosamine-6-phosphate bridges and stabilizes the SpNanR tetramer. SpNanR binds its DNA recognition sequence with nanomolar affinity. Notably, the effector N-acetylmannosamine-6-phosphate does not affect the affinity of SpNanR for DNA. The DNA-binding domains are not structurally coupled to the sugar isomerase domains, explaining why N-acetylmannosamine-6-phosphate binding does not affect DNA binding. Structural analysis reveals that sequence specificity arises through distortion of B-DNA and an unusual \u03c0-stack formed by two arginine residues in the minor groove, while affinity is driven by backbone contacts. We propose a mechanism by which S. pneumoniae regulates sialic acid metabolism, consistent with our biophysical experiments and in vivo regulatory behavior. These findings define a unique activation mechanism for an RpiR regulator and provide new insights into carbohydrate-responsive gene regulation in pneumococci.<\/jats:p>","DOI":"10.1093\/nar\/gkag953","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:17:00Z","timestamp":1790335020000},"source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of NanR transcriptional activation of sialic acid metabolism in\n                    <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8275-3510","authenticated-orcid":false,"given":"David M","family":"Wood","sequence":"first","affiliation":[{"name":"Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury , PO Box 4800, Christchurch 8140 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashleigh S","family":"Johns","sequence":"additional","affiliation":[{"name":"Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury , PO Box 4800, Christchurch 8140 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary D","family":"Tillett","sequence":"additional","affiliation":[{"name":"Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury , PO Box 4800, Christchurch 8140 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather L","family":"Shearer","sequence":"additional","affiliation":[{"name":"M\u0101tai H\u0101ora\u2014Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago Christchurch , Christchurch 8041 ,","place":["New 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Institute, University of Melbourne , Parkville, Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M","family":"Allison","sequence":"additional","affiliation":[{"name":"Biomolecular Interaction Centre, School of Physical and Chemical Sciences, University of Canterbury , Christchurch 8041 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel\u00a0A","family":"North","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, University of Sydney , New South Wales 2006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E","family":"Pace","sequence":"additional","affiliation":[{"name":"M\u0101tai H\u0101ora\u2014Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago Christchurch , Christchurch 8041 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borries","family":"Demeler","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive , Lethbridge, AB T1K 3M4 ,","place":["Canada"]},{"name":"Department of Chemistry and Biochemistry, University of Montana , Missoula, MT 59812 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-3729","authenticated-orcid":false,"given":"Mark B","family":"Hampton","sequence":"additional","affiliation":[{"name":"M\u0101tai H\u0101ora\u2014Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago Christchurch , Christchurch 8041 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renwick C J","family":"Dobson","sequence":"additional","affiliation":[{"name":"Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury , PO Box 4800, Christchurch 8140 ,","place":["New Zealand"]},{"name":"Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne , Parkville, Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R","family":"Horne","sequence":"additional","affiliation":[{"name":"Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury , PO Box 4800, Christchurch 8140 ,","place":["New Zealand"]},{"name":"Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3050 ,","place":["Australia"]},{"name":"Department of Medical Biology, University of Melbourne , Parkville, Victoria 3052 ,","place":["Australia"]},{"name":"Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University , Victoria 3052 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