{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:39:24Z","timestamp":1789533564774,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T00:00:00Z","timestamp":1478476800000},"content-version":"vor","delay-in-days":3054,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,8]]},"DOI":"10.1093\/nar\/gkn400","type":"journal-article","created":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T20:34:20Z","timestamp":1214685260000},"page":"4390-4401","source":"Crossref","is-referenced-by-count":42,"title":["A protein functional leap: how a single mutation reverses the function of the transcription regulator TetR"],"prefix":"10.1093","volume":"36","author":[{"given":"Marcus","family":"Resch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Striegl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Maria","family":"Henssler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhumati","family":"Sevvana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Egerer-Sieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Schiltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hillen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves A.","family":"Muller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"key\n\t\t\t\t20170510124622_B1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-86659-3","volume-title":"Evolution by Gene Duplication.","author":"Ohno","year":"1970"},{"key":"key\n\t\t\t\t20170510124622_B2","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1126\/science.1142819","article-title":"Crystal structure of an ancient protein: evolution by conformational epistasis","volume":"317","author":"Ortlund","year":"2007","journal-title":"Science"},{"key":"key\n\t\t\t\t20170510124622_B3","doi-asserted-by":"crossref","first-page":"17004","DOI":"10.1073\/pnas.0707158104","article-title":"Ohnos dilemma: evolution of new genes under continuous selection","volume":"104","author":"Bergthorsson","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20170510124622_B4","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1126\/science.290.5494.1151","article-title":"The evolutionary fate and consequences of duplicate genes","volume":"290","author":"Lynch","year":"2000","journal-title":"Science"},{"key":"key\n\t\t\t\t20170510124622_B5","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1126\/science.271.5253.1247","article-title":"Crystal structure of the lactose operon repressor and its complexes with DNA and inducer","volume":"271","author":"Lewis","year":"1996","journal-title":"Science"},{"key":"key\n\t\t\t\t20170510124622_B6","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0092-8674(95)90243-0","article-title":"Mechanism of corepressor-mediated specific DNA binding by the purine repressor","volume":"83","author":"Schumacher","year":"1995","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170510124622_B7","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1110\/ps.4050102","article-title":"Fine-tuning function: correlation of hinge domain interactions with functional distinctions between LacI and PurR","volume":"11","author":"Swint-Kruse","year":"2002","journal-title":"Protein Sci."},{"key":"key\n\t\t\t\t20170510124622_B8","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/78907","article-title":"A closer view of the conformation of the Lac repressor bound to operator","volume":"7","author":"Bell","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"key\n\t\t\t\t20170510124622_B9","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1006\/jmbi.1994.0138","article-title":"The complex formed between Tet repressor and tetracycline-Mg2+ reveals mechanism of antibiotic resistance","volume":"247","author":"Kisker","year":"1995","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B10","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1006\/abio.1995.0006","article-title":"Thermodynamic analysis of tetracycline-mediated induction of Tet repressor by a quantitative methylation protection assay","volume":"232","author":"Lederer","year":"1995","journal-title":"Anal. Biochem."},{"key":"key\n\t\t\t\t20170510124622_B11","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1006\/jmbi.1998.1775","article-title":"Conformational changes of the Tet repressor induced by tetracycline trapping","volume":"279","author":"Orth","year":"1998","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B12","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/73324","article-title":"Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system","volume":"7","author":"Orth","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"key\n\t\t\t\t20170510124622_B13","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1002\/1521-3773(20000616)39:12<2042::AID-ANIE2042>3.0.CO;2-C","article-title":"The tetracycline repressor-A paradigm for a biological switch","volume":"39","author":"Saenger","year":"2000","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"key\n\t\t\t\t20170510124622_B14","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1111\/j.1742-4658.2005.04868.x","article-title":"Tet repressor mutants with altered effector binding and allostery","volume":"272","author":"Henssler","year":"2005","journal-title":"FEBS J."},{"key":"key\n\t\t\t\t20170510124622_B15","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1093\/nar\/gkh200","article-title":"Two mutations in the tetracycline repressor change the inducer anhydrotetracycline to a corepressor","volume":"32","author":"Kamionka","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170510124622_B16","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/j.1365-2958.2004.04159.x","article-title":"Activity reversal of Tet repressor caused by single amino acid exchanges","volume":"53","author":"Scholz","year":"2004","journal-title":"Mol. Microbiol."},{"key":"key\n\t\t\t\t20170510124622_B17","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1046\/j.1432-1033.2003.03694.x","article-title":"Gene regulation by tetracyclines. Constraints of resistance regulation in bacteria shape TetR for application in eukaryotes","volume":"270","author":"Berens","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"key\n\t\t\t\t20170510124622_B18","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev.genet.36.041002.120114","article-title":"Studying gene function in eukaryotes by conditional gene inactivation","volume":"36","author":"Gossen","year":"2002","journal-title":"Annu. Rev. Genet."},{"key":"key\n\t\t\t\t20170510124622_B19","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0022-2836(90)90126-7","article-title":"Genetic studies of the lac repressor. XIII. Extensive amino acid replacements generated by the use of natural and synthetic nonsense suppressors","volume":"212","author":"Kleina","year":"1990","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B20","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1006\/jmbi.1996.0479","article-title":"Genetic studies of the Lac repressor. XV: 4000 single amino acid substitutions and analysis of the resulting phenotypes on the basis of the protein structure","volume":"261","author":"Suckow","year":"1996","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B21","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.jmb.2007.02.030","article-title":"How an agonist peptide mimics the antibiotic tetracycline to induce tet-repressor","volume":"368","author":"Luckner","year":"2007","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B22","doi-asserted-by":"crossref","first-page":"W668","DOI":"10.1093\/nar\/gkh371","article-title":"DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data","volume":"32","author":"Whitmore","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170510124622_B23","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1107\/S0021889893005588","article-title":"Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants","volume":"26","author":"Kabsch","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B24","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1107\/S0907444905001617","article-title":"Likelihood-enhanced fast translation functions","volume":"61","author":"McCoy","year":"2005","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B25","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1107\/S0907444900005072","article-title":"Maximum-likelihood density modification","volume":"56","author":"Terwilliger","year":"2000","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B26","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":"key\n\t\t\t\t20170510124622_B27","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1107\/S0907444996012255","article-title":"Refinement of macromolecular structures by the maximum-likelihood method","volume":"53","author":"Murshudov","year":"1997","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B28","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1107\/S0907444900014736","article-title":"Use of TLS parameters to model anisotropic displacements in macromolecular refinement","volume":"57","author":"Winn","year":"2001","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B29","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1107\/S0907444905001897","article-title":"A molecular viewer for the analysis of TLS rigid-body motion in macromolecules","volume":"61","author":"Painter","year":"2005","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B30","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1107\/S0907444906005270","article-title":"Optimal description of a protein structure in terms of multiple groups undergoing TLS motion","volume":"62","author":"Painter","year":"2006","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B31","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1107\/S0021889893002729","article-title":"TLSANL: TLS parameter-analysis program for segmented anisotropic refinement of macromolecular structures","volume":"26","author":"Howlin","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B32","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: programs for protein crystallography","volume":"50","author":"CCP4","year":"1994","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B33","volume-title":"The PyMOL Molecular Graphics System.","author":"DeLano","year":"2003"},{"key":"key\n\t\t\t\t20170510124622_B34","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1126\/science.7792603","article-title":"Transcriptional activation by tetracyclines in mammalian cells","volume":"268","author":"Gossen","year":"1995","journal-title":"Science"},{"key":"key\n\t\t\t\t20170510124622_B35","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170510124622_B36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.jmb.2006.06.035","article-title":"Two-way interdomain signal transduction in tetracycline repressor","volume":"361","author":"Reichheld","year":"2006","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B37","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/327591a0","article-title":"The crystal structure of trp aporepressor at 1.8 A shows how binding tryptophan enhances DNA affinity","volume":"327","author":"Zhang","year":"1987","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170510124622_B38","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1006\/jmbi.1996.0607","article-title":"The effect of self-association on the interaction of the Escherichia coli regulatory protein TyrR with DNA","volume":"263","author":"Bailey","year":"1996","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B39","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1006\/jmbi.2000.4249","article-title":"Multiple disordered loops function in corepressor-induced dimerization of the biotin repressor","volume":"304","author":"Kwon","year":"2000","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1006\/jmbi.1996.0093","article-title":"Structure of the oligomerization and L-arginine binding domain of the arginine repressor of Escherichia coli","volume":"256","author":"Van Duyne","year":"1996","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B41","doi-asserted-by":"crossref","first-page":"6045","DOI":"10.1073\/pnas.111128198","article-title":"Corepressor-induced organization and assembly of the biotin repressor: a model for allosteric activation of a transcriptional regulator","volume":"98","author":"Weaver","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20170510124622_B42","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1073\/pnas.98.4.1507","article-title":"The quorum-sensing transcriptional regulator TraR requires its cognate signaling ligand for protein folding, protease resistance, and dimerization","volume":"98","author":"Zhu","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20170510124622_B43","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nsb0497-269","article-title":"Improved R-factors for diffraction data analysis in macromolecular crystallography","volume":"4","author":"Diederichs","year":"1997","journal-title":"Nat. Struct. Biol."},{"key":"key\n\t\t\t\t20170510124622_B44","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"key\n\t\t\t\t20170510124622_B45","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0022-2836(86)90437-7","article-title":"Kinetic and equilibrium characterization of the Tet repressor-tetracycline complex by fluorescence measurements. Evidence for divalent metal ion requirement and energy transfer","volume":"187","author":"Takahashi","year":"1986","journal-title":"J. Mol. Biol."},{"key":"key\n\t\t\t\t20170510124622_B46","doi-asserted-by":"crossref","first-page":"10914","DOI":"10.1021\/bi001018p","article-title":"Tet repressor induction without Mg 2+","volume":"39","author":"Scholz","year":"2000","journal-title":"Biochemistry"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/36\/13\/4390\/16747908\/gkn400.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T10:40:11Z","timestamp":1522665611000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkn400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,28]]},"references-count":46,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2008,6,28]]},"published-print":{"date-parts":[[2008,8]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkn400","relation":{},"ISSN":["1362-4962","0305-1048"],"issn-type":[{"value":"1362-4962","type":"electronic"},{"value":"0305-1048","type":"print"}],"subject":[],"published":{"date-parts":[[2008,6,28]]}}}