Gene Symbol: P91278ORF_002
Description: tetracycline repressor protein TetR
Species: causative agent of fish pasteurellosis
Hinrichs W, Kisker C, D vel M, M ller A, Tovar K, Hillen W, et al
. Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance. Science. 1994;264:418-20 pubmed
..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...
Orth P, Schnappinger D, Sum P, Ellestad G, Hillen W, Saenger W, et al
. Crystal structure of the tet repressor in complex with a novel tetracycline, 9-(N,N-dimethylglycylamido)- 6-demethyl-6-deoxy-tetracycline. J Mol Biol. 1999;285:455-61 pubmed publisher
Orth P, Schnappinger D, Hillen W, Saenger W, Hinrichs W. Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system. Nat Struct Biol. 2000;7:215-9 pubmed publisher
..This forces a pendulum-like motion of helix a4, which increases the separation of the attached DNA binding domains by 3 A, abolishing the affinity of TetR for its operator DNA...
Tovar K, Ernst A, Hillen W. Identification and nucleotide sequence of the class E tet regulatory elements and operator and inducer binding of the encoded purified Tet repressor. Mol Gen Genet. 1988;215:76-80 pubmed
..This property is lost in the presence of tetracycline. The relationship of the tetRE sequence to four known tetracycline resistance determinants is discussed. ..
Kisker C, Hinrichs W, Tovar K, Hillen W, Saenger W. The complex formed between Tet repressor and tetracycline-Mg2+ reveals mechanism of antibiotic resistance. J Mol Biol. 1995;247:260-80 pubmed
..The detailed view of the Tc-binding pocket and the interactions between the antibiotic and the repressor offers the first solid basis for rational tetracycline design, with the aim of circumventing resistance...
Orth P, Cordes F, Schnappinger D, Hillen W, Saenger W, Hinrichs W. Conformational changes of the Tet repressor induced by tetracycline trapping. J Mol Biol. 1998;279:439-47 pubmed publisher
..The alpha-helix 4 connects the DNA-binding domain (alpha-helices 1 to 3) to the rigid TetR core, and thus regulates gene expression through its respective orientations...
Orth P, Saenger W, Hinrichs W. Tetracycline-chelated Mg2+ ion initiates helix unwinding in Tet repressor induction. Biochemistry. 1999;38:191-8 pubmed publisher
..They simultaneously close the tunnel entrance and cause the DNA-binding domains to adopt a nonbinding conformation, leading to release of operator DNA and expression of the genes responsible for resistance...
Aleksandrov A, Proft J, Hinrichs W, Simonson T. Protonation patterns in tetracycline:tet repressor recognition: simulations and experiments. Chembiochem. 2007;8:675-85 pubmed publisher
..These insights and the modeling techniques employed should be of interest for engineering improved TetR ligands and improved TetR proteins for gene regulation, as well as for drug design...