{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:52:39Z","timestamp":1789516359642,"version":"build-2803163510"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00208153"],"award-info":[{"award-number":["RS-2023-00208153"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1I1A1A01068105"],"award-info":[{"award-number":["2022R1I1A1A01068105"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002507","name":"Kangwon National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002507","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Uric acid (UA)-responsive transcriptional regulators (UrtRs), which belong to the multiple antibiotic resistance regulator (MarR) superfamily, transcriptionally coordinate virulence and metabolism in bacteria by modulating interactions with operator DNA in response to UA. To elucidate the transcriptional regulatory mechanism of UrtR, we structurally analyzed UrtR proteins, including PecS, MftR, and HucR, alone and in complex with UA or DNA. UrtR contains a dimerization domain (DD) and a winged helix-turn-helix domain (wHTHD) and forms a homodimer primarily via the DD, as observed for other MarR superfamily proteins. However, UrtRs are characterized by a unique N-terminal \u03b1-helix, which contributes to dimerization and UA recognition. In the absence of UA, the UrtR dimer symmetrically binds to the operator double-stranded DNA (dsDNA) by inserting its \u03b14 recognition helix and \u03b2-stranded wing within the wHTHD into the major and minor grooves of dsDNA, respectively. Upon exposure to UA, UrtR accommodates UA in the intersubunit pocket between the DD and wHTHD. UA binding induces a conformational change in the major groove-binding core element of the UrtR wHTHD, generating a DNA binding-incompatible structure. This local allosteric mechanism of UrtR completely differs from that generally observed in other MarR superfamily members, in which the entire wHTHD undergoes effector-responsive global shifts.<\/jats:p>","DOI":"10.1093\/nar\/gkae922","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T10:29:38Z","timestamp":1730456978000},"page":"13192-13205","source":"Crossref","is-referenced-by-count":14,"title":["Structural basis of transcriptional regulation by UrtR in response to uric acid"],"prefix":"10.1093","volume":"52","author":[{"given":"Wan\u00a0Seok","family":"Song","sequence":"first","affiliation":[{"name":"Institute of Bioscience and Biotechnology, Kangwon National University , 1 Kangwondaehakgil,\u00a0Chuncheon\u00a0 24341 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Uk","family":"Ki","sequence":"additional","affiliation":[{"name":"Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University , 1 Kangwondaehakgil, Chuncheon\u00a0 24341 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye\u00a0Yeon","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University , 1 Kangwondaehakgil, Chuncheon\u00a0 24341 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oh\u00a0Hyun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Sungkyunkwan University , 2066 Seobu-ro,\u00a0Suwon\u00a0 16419 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbaek","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Sungkyunkwan University , 2066 Seobu-ro,\u00a0Suwon\u00a0 16419 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0777-0457","authenticated-orcid":false,"given":"Sung-il","family":"Yoon","sequence":"additional","affiliation":[{"name":"Institute of Bioscience and Biotechnology, Kangwon National University , 1 Kangwondaehakgil,\u00a0Chuncheon\u00a0 24341 ,","place":["Republic of Korea"]},{"name":"Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University , 1 Kangwondaehakgil, Chuncheon\u00a0 24341 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"2024112721450690000_B1","doi-asserted-by":"crossref","first-page":"R142","DOI":"10.1016\/j.cub.2013.01.013","article-title":"MarR family transcription factors","volume":"23","author":"Grove","year":"2013","journal-title":"Curr. Biol."},{"key":"2024112721450690000_B2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.csbj.2017.06.001","article-title":"Regulation of metabolic pathways by MarR family transcription factors","volume":"15","author":"Grove","year":"2017","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"2024112721450690000_B3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/jmcb\/mjq021","article-title":"Molecular mechanisms of ligand-mediated attenuation of DNA binding by MarR family transcriptional regulators","volume":"2","author":"Perera","year":"2010","journal-title":"J. Mol. Cell Biol."},{"key":"2024112721450690000_B4","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.3390\/microorganisms11081936","article-title":"MarR family transcriptional regulators and their roles in plant-interacting bacteria","volume":"11","author":"Nazaret","year":"2023","journal-title":"Microorganisms"},{"key":"2024112721450690000_B5","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","article-title":"Pfam: the protein families database in 2021","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2024112721450690000_B6","first-page":"51","article-title":"Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins","volume":"8","author":"Wilkinson","year":"2006","journal-title":"Curr. Iss. Mol. Biol."},{"key":"2024112721450690000_B7","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/pro.588","article-title":"MarR homologs with urate-binding signature","volume":"20","author":"Perera","year":"2011","journal-title":"Protein Sci."},{"key":"2024112721450690000_B8","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/0006-2952(80)90108-2","article-title":"Xanthine oxidase increase in polymorphonuclear leucocytes and macrophages in mice in three pathological situations","volume":"29","author":"Tubaro","year":"1980","journal-title":"Biochem. Pharmacol."},{"key":"2024112721450690000_B9","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1128\/IAI.01124-12","article-title":"Role of host xanthine oxidase in infection due to enteropathogenic and shiga-toxigenic Escherichia coli","volume":"81","author":"Crane","year":"2013","journal-title":"Infect. Immun."},{"key":"2024112721450690000_B10","doi-asserted-by":"crossref","first-page":"4933","DOI":"10.1128\/IAI.72.9.4933-4939.2004","article-title":"Role of xanthine oxidoreductase as an antimicrobial agent","volume":"72","author":"Martin","year":"2004","journal-title":"Infect. Immun."},{"key":"2024112721450690000_B11","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1073\/pnas.1320393111","article-title":"Evolutionary history and metabolic insights of ancient mammalian uricases","volume":"111","author":"Kratzer","year":"2014","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2024112721450690000_B12","doi-asserted-by":"crossref","first-page":"7508","DOI":"10.1128\/JB.00553-08","article-title":"PecS is a global regulator of the symptomatic phase in the phytopathogenic bacterium Erwinia chrysanthemi 3937","volume":"190","author":"Hommais","year":"2008","journal-title":"J. Bacteriol."},{"key":"2024112721450690000_B13","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/mpp.12549","article-title":"Transcriptome analysis of the Dickeya dadantii PecS regulon during the early stages of interaction with Arabidopsis thaliana","volume":"19","author":"Pedron","year":"2018","journal-title":"Mol. Plant Pathol."},{"key":"2024112721450690000_B14","doi-asserted-by":"crossref","first-page":"e0023722","DOI":"10.1128\/jb.00237-22","article-title":"The global regulator MftR controls virulence and siderophore production in Burkholderia thailandensis","volume":"204","author":"Thapa","year":"2022","journal-title":"J. Bacteriol."},{"key":"2024112721450690000_B15","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1021\/bi500219t","article-title":"Ligand-binding pocket bridges DNA-binding and dimerization domains of the urate-responsive MarR homologue MftR from Burkholderia thailandensis","volume":"53","author":"Gupta","year":"2014","journal-title":"Biochemistry"},{"key":"2024112721450690000_B16","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1021\/acschembio.7b00681","article-title":"Global awakening of cryptic biosynthetic gene clusters in Burkholderia thailandensis","volume":"12","author":"Gupta","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"2024112721450690000_B17","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1128\/JB.184.3.654-665.2002","article-title":"Characterization of indigoidine biosynthetic genes in Erwinia chrysanthemi and role of this blue pigment in pathogenicity","volume":"184","author":"Reverchon","year":"2002","journal-title":"J. Bacteriol."},{"key":"2024112721450690000_B18","doi-asserted-by":"crossref","first-page":"e0047822","DOI":"10.1128\/jb.00478-22","article-title":"Transcription factor PecS mediates Agrobacterium fabrum fitness and survival","volume":"205","author":"Nwokocha","year":"2023","journal-title":"J. Bacteriol."},{"key":"2024112721450690000_B19","doi-asserted-by":"crossref","first-page":"51442","DOI":"10.1074\/jbc.M405586200","article-title":"HucR, a novel uric acid-responsive member of the MarR family of transcriptional regulators from Deinococcus radiodurans","volume":"279","author":"Wilkinson","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2024112721450690000_B20","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3390\/antibiotics8040160","article-title":"Do global regulators hold the key to production of bacterial secondary metabolites?","volume":"8","author":"Thapa","year":"2019","journal-title":"Antibiotics (Basel)"},{"key":"2024112721450690000_B21","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jmb.2010.07.053","article-title":"Urate is a ligand for the transcriptional regulator PecS","volume":"402","author":"Perera","year":"2010","journal-title":"J. Mol. Biol."},{"key":"2024112721450690000_B22","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jmb.2006.05.005","article-title":"The crystal structure of the transcriptional regulator HucR from Deinococcus radiodurans reveals a repressor preconfigured for DNA binding","volume":"360","author":"Bordelon","year":"2006","journal-title":"J. Mol. Biol."},{"key":"2024112721450690000_B23","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bbrc.2022.05.034","article-title":"The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound","volume":"615","author":"Rho","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2024112721450690000_B24","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.jmb.2009.06.002","article-title":"Mechanism for attenuation of DNA binding by MarR family transcriptional regulators by small molecule ligands","volume":"390","author":"Perera","year":"2009","journal-title":"J. Mol. Biol."},{"key":"2024112721450690000_B25","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.3390\/ijms23031882","article-title":"Structural and biochemical analysis of the furan aldehyde reductase YugJ from Bacillus subtilis","volume":"23","author":"Cho","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2024112721450690000_B26","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski","year":"1997","journal-title":"Methods Enzymol."},{"key":"2024112721450690000_B27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"2024112721450690000_B28","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1107\/S0907444909012098","article-title":"Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard","volume":"65","author":"Terwilliger","year":"2009","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"2024112721450690000_B29","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"2024112721450690000_B30","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","article-title":"Phaser crystallographic software","volume":"40","author":"McCoy","year":"2007","journal-title":"J. Appl. Crystallogr."},{"key":"2024112721450690000_B31","first-page":"607","article-title":"Fluorescence polarization analysis of protein\u2013DNA and protein\u2013protein interactions","volume":"10","author":"Lundblad","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"2024112721450690000_B32","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1039\/c0mb00086h","article-title":"Urate-responsive MarR homologs from Burkholderia","volume":"6","author":"Grove","year":"2010","journal-title":"Mol. Biosyst."},{"key":"2024112721450690000_B33","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1021\/acschembio.6b00168","article-title":"pH-dependent DNA distortion and repression of gene expression by Pectobacterium atrosepticum PecS","volume":"11","author":"Deochand","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"2024112721450690000_B34","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1038\/s41598-019-39095-4","article-title":"A role for Vibrio vulnificus PecS during hypoxia","volume":"9","author":"Bhattacharyya","year":"2019","journal-title":"Sci. Rep."},{"key":"2024112721450690000_B35","doi-asserted-by":"crossref","first-page":"W240","DOI":"10.1093\/nar\/gkp358","article-title":"Web 3DNA\u2014a web server for the analysis, reconstruction, and visualization of three-dimensional nucleic-acid structures","volume":"37","author":"Zheng","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2024112721450690000_B36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.bbrc.2022.03.133","article-title":"Structure-based molecular characterization of the YetL transcription factor from Bacillus subtilis","volume":"607","author":"Park","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2024112721450690000_B37","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1128\/JB.02224-12","article-title":"Mutational analysis of the multiple-antibiotic resistance regulator MarR reveals a ligand binding pocket at the interface between the dimerization and DNA binding domains","volume":"195","author":"Duval","year":"2013","journal-title":"J. Bacteriol."},{"key":"2024112721450690000_B38","doi-asserted-by":"crossref","first-page":"4723","DOI":"10.1093\/nar\/gkp496","article-title":"ST1710-DNA complex crystal structure reveals the DNA binding mechanism of the MarR family of regulators","volume":"37","author":"Kumarevel","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2024112721450690000_B39","doi-asserted-by":"crossref","first-page":"22178","DOI":"10.1074\/jbc.M111.245258","article-title":"Crystal structures of SlyA protein, a master virulence regulator of Salmonella, in free and DNA-bound states","volume":"286","author":"Dolan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2024112721450690000_B40","doi-asserted-by":"crossref","first-page":"6471","DOI":"10.1038\/s41598-017-01705-4","article-title":"Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis","volume":"7","author":"Gao","year":"2017","journal-title":"Sci. Rep."},{"key":"2024112721450690000_B41","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1021\/jacs.6b11438","article-title":"Structural insights into the redox-sensing mechanism of MarR-type regulator AbfR","volume":"139","author":"Liu","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"2024112721450690000_B42","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1074\/jbc.RA118.003561","article-title":"Structural basis of transcriptional regulation by CouR, a repressor of coumarate catabolism, in Rhodopseudomonas palustris","volume":"293","author":"Cogan","year":"2018","journal-title":"J. Biol. Chem."},{"key":"2024112721450690000_B43","doi-asserted-by":"crossref","first-page":"13243","DOI":"10.1074\/jbc.M115.712067","article-title":"How aromatic compounds block DNA binding of HcaR catabolite regulator","volume":"291","author":"Kim","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2024112721450690000_B44","doi-asserted-by":"crossref","first-page":"37703","DOI":"10.1074\/jbc.M112.388611","article-title":"The oxidation-sensing regulator (MosR) is a new redox-dependent transcription factor in Mycobacterium tuberculosis","volume":"287","author":"Brugarolas","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2024112721450690000_B45","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s42003-021-01987-5","article-title":"Heme controls the structural rearrangement of its sensor protein mediating the hemolytic bacterial survival","volume":"4","author":"Nishinaga","year":"2021","journal-title":"Commun. Biol."},{"key":"2024112721450690000_B46","doi-asserted-by":"crossref","first-page":"e00009-19","DOI":"10.1128\/mBio.00009-19","article-title":"The evolution of SlyA\/RovA transcription factors from repressors to countersilencers in Enterobacteriaceae","volume":"10","author":"Will","year":"2019","journal-title":"mBio"},{"key":"2024112721450690000_B47","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bpc.2011.05.007","article-title":"Allostery in the lac operon: population selection or induced dissociation","volume":"159","author":"Sharp","year":"2011","journal-title":"Biophys. Chem."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/advance-article-pdf\/doi\/10.1093\/nar\/gkae922\/60836106\/gkae922.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/advance-article-pdf\/doi\/10.1093\/nar\/gkae922\/60836106\/gkae922.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T21:46:02Z","timestamp":1732743962000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/52\/21\/13192\/7850960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,1]]},"references-count":47,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11,1]]},"published-print":{"date-parts":[[2024,11,27]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkae922","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,11,27]]},"published":{"date-parts":[[2024,11,1]]}}}