{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:40:40Z","timestamp":1791225640263,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n                    regulator MarR represses the multiple-antibiotic resistance operon\n                    <jats:italic>marRAB<\/jats:italic>\n                    and responds to phenolic compounds, including sodium salicylate, which inhibit its activity. Crystals obtained in the presence of a high concentration of salicylate indicated two possible salicylate sites, SAL-A and SAL-B. However, it was unclear whether these sites were physiologically significant or were simply a result of the crystallization conditions. A study carried out on MarR homologue MTH313 suggested the presence of a salicylate binding site buried at the interface between the dimerization and the DNA-binding domains. Interestingly, the authors of the study indicated a similar pocket conserved in the MarR structure. Since no mutagenesis analysis had been performed to test which amino acids were essential in salicylate binding, we examined the role of residues that could potentially interact with salicylate. We demonstrated that mutations in residues shown as interacting with salicylate at SAL-A and SAL-B in the MarR-salicylate structure had no effect on salicylate binding, indicating that these sites were not the physiological regulatory sites. However, some of these residues (P57, R86, M74, and R77) were important for DNA binding. Furthermore, mutations in residues R16, D26, and K44 significantly reduced binding to both salicylate and 2,4-dinitrophenol, while a mutation in residue H19 impaired the binding to 2,4-dinitrophenol only. These findings indicate, as for MTH313, the presence of a ligand binding pocket located between the dimerization and DNA binding domains.\n                  <\/jats:p>","DOI":"10.1128\/jb.02224-12","type":"journal-article","created":{"date-parts":[[2013,5,18]],"date-time":"2013-05-18T02:08:34Z","timestamp":1368842914000},"page":"3341-3351","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"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"],"prefix":"10.1128","volume":"195","author":[{"given":"Val\u00e9rie","family":"Duval","sequence":"first","affiliation":[{"name":"Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"McMurry","sequence":"additional","affiliation":[{"name":"Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Foster","sequence":"additional","affiliation":[{"name":"Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Head","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart B.","family":"Levy","sequence":"additional","affiliation":[{"name":"Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.mib.2009.07.003","article-title":"Structure, function and inhibition of RND efflux pumps in Gram-negative bacteria: an update","volume":"12","author":"Blair JM","year":"2009","unstructured":"BlairJM PiddockLJ. 2009. Structure, function and inhibition of RND efflux pumps in Gram-negative bacteria: an update. Curr. Opin. Microbiol. 12:512\u2013519.","journal-title":"Curr. Opin. Microbiol."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.12.5416-5422.1988"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fmicb.2011.00189","article-title":"Mechanism and function of the outer membrane channel TolC in multidrug resistance and physiology of enterobacteria","volume":"2","author":"Zgurskaya HI","year":"2011","unstructured":"ZgurskayaHI KrishnamoorthyG NtrehA LuS. 2011. Mechanism and function of the outer membrane channel TolC in multidrug resistance and physiology of enterobacteria. Front. Microbiol. 2:189.","journal-title":"Front. Microbiol."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.2.248"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5456"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.24.7856-7862.1993"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.15.4669-4672.1999"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.13.3890-3902.2001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/90429","article-title":"The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution","volume":"8","author":"Alekshun MN","year":"2001","unstructured":"AlekshunMN LevySB MealyTR SeatonBA HeadJF. 2001. The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution. Nat. Struct. Biol. 8:710\u2013714.","journal-title":"Nat. Struct. Biol."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00371-10"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.12.3467-3474.2000"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.19.6122-6126.1997"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.8.4143-4150.1990"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.4.1026-1031.1993"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.052"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.09.013"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.01.001"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1021\/bi801662s","article-title":"Characterization of the ligand and DNA binding properties of a putative archaeal regulator ST1710","volume":"48","author":"Yu L","year":"2009","unstructured":"YuL FangJ WeiY. 2009. Characterization of the ligand and DNA binding properties of a putative archaeal regulator ST1710. Biochemistry 48:2099\u20132108.","journal-title":"Biochemistry"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.09.016"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","first-page":"8617","DOI":"10.1073\/pnas.0913302107","article-title":"Structural study of TcaR and its complexes with multiple antibiotics from Staphylococcus epidermidis","volume":"107","author":"Chang YM","year":"2010","unstructured":"ChangYM JengWY KoTP YehYJ ChenCK WangAH. 2010. Structural study of TcaR and its complexes with multiple antibiotics from Staphylococcus epidermidis. Proc. Natl. Acad. Sci. U. S. A. 107:8617\u20138622.","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp496"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.10.3303-3306.1999"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.12.3414-3419.1995"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.155.2.531-540.1983"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.8.2089"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00787-09"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(89)90358-2"},{"key":"e_1_3_3_29_2","unstructured":"MillerJH. 1972. \nExperiments in molecular genetics. \nCold Spring Harbor Laboratory Press Cold Spring Harbor NY."},{"key":"e_1_3_3_30_2","doi-asserted-by":"crossref","first-page":"15835","DOI":"10.1073\/pnas.0605224103","article-title":"Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination","volume":"103","author":"Vedadi M","year":"2006","unstructured":"VedadiM NiesenFH Allali-HassaniA FedorovOY FinertyPJJr WasneyGA YeungR ArrowsmithC BallLJ BerglundH HuiR MarsdenBD NordlundP SundstromM WeigeltJ EdwardsAM. 2006. Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination. Proc. Natl. Acad. Sci. U. S. A. 103:15835\u201315840.","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1038\/nprot.2007.321","article-title":"The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability","volume":"2","author":"Niesen FH","year":"2007","unstructured":"NiesenFH BerglundH VedadiM. 2007. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. 2:2212\u20132221.","journal-title":"Nat. Protoc."},{"key":"e_1_3_3_32_2","doi-asserted-by":"crossref","first-page":"37773","DOI":"10.1074\/jbc.M110.143107","article-title":"A novel p53 phosphorylation site within the MDM2 ubiquitination signal: II. A model in which phosphorylation at SER269 induces a mutant conformation to p53","volume":"285","author":"Fraser JA","year":"2010","unstructured":"FraserJA MadhumalarA BlackburnE BramhamJ WalkinshawMD VermaC HuppTR. 2010. A novel p53 phosphorylation site within the MDM2 ubiquitination signal: II. A model in which phosphorylation at SER269 induces a mutant conformation to p53. J. Biol. Chem. 285:37773\u201337786.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_3_33_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ab.2004.04.031","article-title":"Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery","volume":"332","author":"Lo MC","year":"2004","unstructured":"LoMC AulabaughA JinG CowlingR BardJ MalamasM EllestadG. 2004. Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery. Anal. Biochem. 332:153\u2013159.","journal-title":"Anal. Biochem."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb1028s94"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401581"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.16.5131-5133.1999"},{"key":"e_1_3_3_37_2","doi-asserted-by":"crossref","first-page":"17114","DOI":"10.1074\/jbc.M602112200","article-title":"Transcription regulation of ompF and ompC by a single transcription factor, OmpR","volume":"281","author":"Yoshida T","year":"2006","unstructured":"YoshidaT QinL EggerLA InouyeM. 2006. Transcription regulation of ompF and ompC by a single transcription factor, OmpR. J. Biol. Chem. 281:17114\u201317123.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/j.1365-2958.1990.tb00681.x","article-title":"Signal transduction and gene regulation through the phosphorylation of two regulatory components: the molecular basis for the osmotic regulation of the porin genes","volume":"4","author":"Mizuno T","year":"1990","unstructured":"MizunoT MizushimaS. 1990. Signal transduction and gene regulation through the phosphorylation of two regulatory components: the molecular basis for the osmotic regulation of the porin genes. Mol. Microbiol. 4:1077\u20131082.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1865-1868.2000"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.7.1695"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02445-12"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.14.4134-4141.2001"},{"key":"e_1_3_3_43_2","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 IC","year":"2010","unstructured":"PereraIC GroveA. 2010. Molecular mechanisms of ligand-mediated attenuation of DNA binding by MarR family transcriptional regulators. J. Mol. Cell Biol. 2:243\u2013254.","journal-title":"J. Mol. Cell Biol."},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.245258"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn1046"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032684"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00576-08"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150181505"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.02224-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.02224-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T13:32:28Z","timestamp":1627565548000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.02224-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8]]},"references-count":47,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1128\/JB.02224-12"],"URL":"https:\/\/doi.org\/10.1128\/jb.02224-12","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8]]},"assertion":[{"value":"2012-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}