{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:16:12Z","timestamp":1791404172159,"version":"4.3.3"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5157","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1994,4,15]]},"abstract":"<jats:p>The most frequently occurring resistance of Gram-negative bacteria against tetracyclines is triggered by drug recognition of the Tet repressor. This causes dissociation of the repressor-operator DNA complex and enables expression of the resistance protein TetA, which is responsible for active efflux of tetracycline. The 2.5 angstrom resolution crystal structure of the homodimeric Tet repressor complexed with tetracycline-magnesium reveals detailed drug recognition. The orientation of the operator-binding helix-turn-helix motifs of the repressor is inverted in comparison with other DNA binding proteins. The repressor-drug complex is unable to interact with DNA because the separation of the DNA binding motifs is 5 angstroms wider than usually observed.<\/jats:p>","DOI":"10.1126\/science.8153629","type":"journal-article","created":{"date-parts":[[2006,10,6]],"date-time":"2006-10-06T00:01:25Z","timestamp":1160092885000},"page":"418-420","source":"Crossref","is-referenced-by-count":358,"title":["Structure of the Tet Repressor-tetracycline Complex and Regulation of Antibiotic Resistance"],"prefix":"10.1126","volume":"264","author":[{"given":"Winfried","family":"Hinrichs","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Kristallographie, Freie Universitat Berlin, 14195 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kisker","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Kristallographie, Freie Universitat Berlin, 14195 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"D\u00fcvel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Kristallographie, Freie Universitat Berlin, 14195 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Kristallographie, Freie Universitat Berlin, 14195 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlheinz","family":"Tovar","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie und Biochemie der Friedrich-Alexander Universit\u00e4t, Erlangen-N\u00fcrnberg, 91058 Erlangen. Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hillen","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie und Biochemie der Friedrich-Alexander Universit\u00e4t, Erlangen-N\u00fcrnberg, 91058 Erlangen. Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Saenger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Kristallographie, Freie Universitat Berlin, 14195 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3187531"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/0022-2836(92)91065-W","volume":"226","year":"1992","unstructured":"BAUMEISTER, R, CONTACTS BETWEEN TET REPRESSOR AND TET OPERATOR REVEALED BY NEW RECOGNITION SPECIFICITIES OF SINGLE AMINO-ACID REPLACEMENT MUTANTS, JOURNAL OF MOLECULAR BIOLOGY 226: 1257 (1992).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/prot.340140204","volume":"14","year":"1992","unstructured":"BAUMEISTER, R, FUNCTIONAL ROLES OF AMINO-ACID-RESIDUES INVOLVED IN FORMING THE ALPHA-HELIX-TURN-ALPHA-HELIX OPERATOR DNA-BINDING MOTIF OF TET REPRESSOR FROM TN10, PROTEINS-STRUCTURE FUNCTION AND GENETICS 14: 168 (1992).","journal-title":"PROTEINS-STRUCTURE FUNCTION AND GENETICS"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/S0021-9258(18)46038-3","volume":"267","year":"1992","unstructured":"BERENS, C, THE ROLE OF THE N-TERMINUS IN TET REPRESSOR FOR TET OPERATOR BINDING DETERMINED BY A MUTATIONAL ANALYSIS, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 1945 (1992).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0378-1119(83)90046-X","volume":"23","year":"1983","unstructured":"BERTRAND, K.P., OVERLAPPING DIVERGENT PROMOTERS CONTROL EXPRESSION OF TN10 TETRACYCLINE RESISTANCE, GENE 23: 149 (1983).","journal-title":"GENE"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.20.8165"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767389009633"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.235.4787.458"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1107\/S0108768190008059","volume":"46","year":"1990","unstructured":"DAUTER, Z, REFINEMENT OF GLUCOSE-ISOMERASE FROM STREPTOMYCES-ALBUS AT 1.65-A WITH DATA FROM AN IMAGING PLATE, ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE 46: 833 (1990).","journal-title":"ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1128\/AAC.35.8.1591","volume":"35","year":"1991","unstructured":"DEGENKOLB, J, STRUCTURAL REQUIREMENTS OF TETRACYCLINE-TET REPRESSOR INTERACTION - DETERMINATION OF EQUILIBRIUM BINDING CONSTANTS FOR TETRACYCLINE ANALOGS WITH THE TET REPRESSOR, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 35: 1591 (1991).","journal-title":"ANTIMICROBIAL AGENTS AND CHEMOTHERAPY"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/353715a0","volume":"353","year":"1991","unstructured":"HARRISON, S.C., A STRUCTURAL TAXONOMY OF DNA-BINDING DOMAINS, NATURE 353: 715 (1991).","journal-title":"NATURE"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1128\/jb.175.4.1206-1210.1993","volume":"175","year":"1993","unstructured":"HECHT, B, NONINDUCIBLE TET REPRESSOR MUTATIONS MAP FROM THE OPERATOR BINDING MOTIF TO THE C-TERMINUS, JOURNAL OF BACTERIOLOGY 175: 1206 (1993).","journal-title":"JOURNAL OF BACTERIOLOGY"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0022-2836(88)90274-4","volume":"202","year":"1988","unstructured":"HEUER, C, TET REPRESSOR TET OPERATOR CONTACTS PROBED BY OPERATOR DNA-MODIFICATION INTERFERENCE STUDIES, JOURNAL OF MOLECULAR BIOLOGY 202: 407 (1988).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0022-2836(83)80166-1","volume":"169","year":"1983","unstructured":"HILLEN, W, CONTROL OF EXPRESSION OF THE TN10-ENCODED TETRACYCLINE RESISTANCE GENES - EQUILIBRIUM AND KINETIC INVESTIGATION OF THE REGULATORY REACTIONS, JOURNAL OF MOLECULAR BIOLOGY 169: 707 (1983).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0022-2836(84)80037-6","volume":"172","year":"1984","unstructured":"HILLEN, W, CONTROL OF EXPRESSION OF THE TN10-ENCODED TETRACYCLINE RESISTANCE OPERON .2. INTERACTION OF RNA-POLYMERASE AND TET REPRESSOR WITH THE TET OPERON REGULATORY REGION, JOURNAL OF MOLECULAR BIOLOGY 172: 185 (1984).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_16_1","first-page":"332","volume":"78","year":"1985","unstructured":"Hlavka, J. J., Handbook of Experimental Pharmacology 78: 332 (1985).","journal-title":"Handbook of Experimental Pharmacology"},{"key":"e_1_2_1_17_1","first-page":"6226","volume":"82","year":"1985","unstructured":"ISACKSON, P.J., DOMINANT NEGATIVE MUTATIONS IN THE TN10 TET REPRESSOR - EVIDENCE FOR USE OF THE CONSERVED HELIX-TURN-HELIX MOTIF IN DNA-BINDING, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 82: 6226 (1985).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889878013308"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3187530"},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/0014-5793(85)80149-6","volume":"193","year":"1985","unstructured":"KANEKO, M, ENERGETICS OF TETRACYCLINE EFFLUX SYSTEM ENCODED BY TN10 IN ESCHERICHIA-COLI, FEBS LETTERS 193: 194 (1985).","journal-title":"FEBS LETTERS"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0022-2836(92)90134-6","volume":"226","year":"1992","unstructured":"KOSTREWA, D, CRYSTAL-STRUCTURE OF THE FACTOR FOR INVERSION STIMULATION FIS AT 2.0 ANGSTROM RESOLUTION, JOURNAL OF MOLECULAR BIOLOGY 226: 209 (1992).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889891004399"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.1432-1033.1990.tb15662.x","volume":"194","year":"1990","unstructured":"LAMERICHS, RMJN, ASSIGNMENT OF THE H-1-NMR SPECTRUM OF A LAC REPRESSOR HEADPIECE-OPERATOR COMPLEX IN H2O AND IDENTIFICATION OF NOES - CONSEQUENCES FOR PROTEIN-DNA INTERACTION, EUROPEAN JOURNAL OF BIOCHEMISTRY 194: 629 (1990).","journal-title":"EUROPEAN JOURNAL OF BIOCHEMISTRY"},{"key":"e_1_2_1_24_1","first-page":"7947","volume":"85","year":"1988","unstructured":"LEHMING, N, RECOGNITION HELICES OF LAC-REPRESSOR AND LAMBDA-REPRESSOR ARE ORIENTED IN OPPOSITE DIRECTIONS AND RECOGNIZE SIMILAR DNA-SEQUENCES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 7947 (1988).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7071602"},{"key":"e_1_2_1_26_1","first-page":"191","year":"1984","unstructured":"Levy, S. B., Antimicrobial Drug Resistance: 191 (1984).","journal-title":"Antimicrobial Drug Resistance"},{"key":"e_1_2_1_27_1","first-page":"418","volume":"54","year":"1988","unstructured":"LEVY, S.B., ASM NEWS 54: 418 (1988).","journal-title":"ASM NEWS"},{"key":"e_1_2_1_28_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0147-619X(80)90101-8","volume":"3","year":"1980","unstructured":"MENDEZ, B, HETEROGENEITY OF TETRACYCLINE RESISTANCE DETERMINANTS, PLASMID 3: 99 (1980).","journal-title":"PLASMID"},{"key":"e_1_2_1_29_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1107\/S002188988708662X","volume":"20","year":"1987","unstructured":"MESSERSCHMIDT, A, CRYSTAL ORIENTATION AND X-RAY PATTERN PREDICTION ROUTINES FOR AREA-DETECTOR DIFFRACTOMETER SYSTEMS IN MACROMOLECULAR CRYSTALLOGRAPHY, JOURNAL OF APPLIED CRYSTALLOGRAPHY 20: 306 (1987).","journal-title":"JOURNAL OF APPLIED CRYSTALLOGRAPHY"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1064"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/335321a0"},{"key":"e_1_2_1_32_1","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/0022-2836(84)90279-1","volume":"180","year":"1984","unstructured":"PARGE, H.E., CRYSTALLIZATION OF AND PRELIMINARY-X-RAY DIFFRACTION DATA FOR TET-REPRESSOR AND THE TET-REPRESSOR TETRACYCLINE COMPLEX, JOURNAL OF MOLECULAR BIOLOGY 180: 1189 (1984).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_33_1","doi-asserted-by":"crossref","first-page":"4849","DOI":"10.1093\/nar\/12.12.4849","volume":"12","year":"1984","unstructured":"POSTLE, K, NUCLEOTIDE-SEQUENCE OF THE REPRESSOR GENE OF THE TN10 TETRACYCLINE RESISTANCE DETERMINANT, NUCLEIC ACIDS RESEARCH 12: 4849 (1984).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80128-7"},{"key":"e_1_2_1_35_1","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/nar\/18.10.2875","volume":"18","year":"1990","unstructured":"SIZEMORE, C, QUANTITATIVE-ANALYSIS OF TN10 TET REPRESSOR BINDING TO A COMPLETE SET OF TET OPERATOR MUTANTS, NUCLEIC ACIDS RESEARCH 18: 2875 (1990).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_36_1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/0022-2836(88)90120-9","volume":"203","year":"1988","unstructured":"SMITH, L.D., MUTATIONS IN THE TN10 TET REPRESSOR THAT INTERFERE WITH INDUCTION - LOCATION OF THE TETRACYCLINE-BINDING DOMAIN, JOURNAL OF MOLECULAR BIOLOGY 203: 949 (1988).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5072.942"},{"key":"e_1_2_1_38_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0022-2836(86)90437-7","volume":"187","year":"1986","unstructured":"TAKAHASHI, M, KINETIC AND EQUILIBRIUM CHARACTERIZATION OF THE TET REPRESSOR TETRACYCLINE COMPLEX BY FLUORESCENCE MEASUREMENTS - EVIDENCE FOR DIVALENT METAL-ION REQUIREMENT AND ENERGY-TRANSFER, JOURNAL OF MOLECULAR BIOLOGY 187: 341 (1986).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_39_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/BF00331306","volume":"215","year":"1988","unstructured":"TOVAR, K, IDENTIFICATION AND NUCLEOTIDE-SEQUENCE OF THE CLASS-E TET REGULATORY ELEMENTS AND OPERATOR AND INDUCER BINDING OF THE ENCODED PURIFIED TET REPRESSOR, MOLECULAR & GENERAL GENETICS 215: 76 (1988).","journal-title":"MOLECULAR & GENERAL GENETICS"},{"key":"e_1_2_1_40_1","doi-asserted-by":"crossref","first-page":"6515","DOI":"10.1093\/nar\/17.16.6515","volume":"17","year":"1989","unstructured":"TOVAR, K, TET REPRESSOR BINDING INDUCED CURVATURE OF TET OPERATOR DNA, NUCLEIC ACIDS RESEARCH 17: 6515 (1989).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_41_1","doi-asserted-by":"crossref","first-page":"7693","DOI":"10.1093\/nar\/12.20.7693","volume":"12","year":"1984","unstructured":"UNGER, B, NUCLEOTIDE-SEQUENCE OF THE REPRESSOR GENE OF THE RA1 TETRACYCLINE RESISTANCE DETERMINANT - STRUCTURAL AND FUNCTIONAL COMPARISON WITH 3 RELATED TET REPRESSOR GENES, NUCLEIC ACIDS RESEARCH 12: 7693 (1984).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_42_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0076-6879(85)15009-3","volume":"115","year":"1985","unstructured":"WANG, B.C., RESOLUTION OF PHASE AMBIGUITY IN MACROMOLECULAR CRYSTALLOGRAPHY, METHODS IN ENZYMOLOGY 115: 90 (1985).","journal-title":"METHODS IN ENZYMOLOGY"},{"key":"e_1_2_1_43_1","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1002\/j.1460-2075.1991.tb04992.x","volume":"10","year":"1991","unstructured":"WISSMANN, A, AMINO-ACIDS DETERMINING OPERATOR BINDING-SPECIFICITY IN THE HELIX-TURN-HELIX MOTIF OF TN10 TET REPRESSOR, EMBO JOURNAL 10: 4145 (1991).","journal-title":"EMBO JOURNAL"},{"key":"e_1_2_1_44_1","doi-asserted-by":"crossref","first-page":"15525","DOI":"10.1016\/S0021-9258(18)55428-4","volume":"265","year":"1990","unstructured":"YAMAGUCHI, A, METAL-TETRACYCLINE\/H+ ANTIPORTER OF ESCHERICHIA-COLI ENCODED BY A TRANSPOSON, TN10 - THE ROLE OF THE CONSERVED DIPEPTIDE, SER65-ASP66, IN TETRACYCLINE TRANSPORT, JOURNAL OF BIOLOGICAL CHEMISTRY 265: 15525 (1990).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_45_1","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/327591a0","volume":"327","year":"1987","unstructured":"ZHANG, R.G., THE CRYSTAL-STRUCTURE OF TRP APOREPRESSOR AT 1.8-A SHOWS HOW BINDING TRYPTOPHAN ENHANCES DNA AFFINITY, NATURE 327: 591 (1987).","journal-title":"NATURE"},{"key":"e_1_2_1_46_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/j.1348-0421.1992.tb02109.x","volume":"36","year":"1992","unstructured":"ZHAO, J, NUCLEOTIDE-SEQUENCE ANALYSIS OF THE CLASS-G TETRACYCLINE RESISTANCE DETERMINANT FROM VIBRIO-ANGUILLARUM, MICROBIOLOGY AND IMMUNOLOGY 36: 1051 (1992).","journal-title":"MICROBIOLOGY AND IMMUNOLOGY"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.8153629","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T05:28:49Z","timestamp":1705296529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.8153629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4,15]]},"references-count":46,"journal-issue":{"issue":"5157","published-print":{"date-parts":[[1994,4,15]]}},"alternative-id":["10.1126\/science.8153629"],"URL":"https:\/\/doi.org\/10.1126\/science.8153629","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4,15]]}}}