Structural changes and binding characteristics of the tetracycline- repressor binding site on induction

Journal of Medicinal Chemistry

Volumn 49, Issue 12, 2006, Pages 3444-3447

  Lanig, Harald ^a   Othersen, Olaf G ^a   Seidel, Ute ^a   Beierlein, Frank R ^a   Exner, Thomas E ^b   Clark, Timothy ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b UNIVERSITY OF KONSTANZ   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANHYDROTETRACYCLINE; REPRESSOR PROTEIN; TETRACYCLINE DERIVATIVE;

ARTICLE; BINDING AFFINITY; COMPUTER SIMULATION; DRUG PROTEIN BINDING; DRUG STRUCTURE; GENETIC SIMILARITY; HYDROGEN BOND; HYDROPHILICITY; LIPOPHILICITY; MOLECULAR DYNAMICS; PHARMACOPHORE; PROTEIN INTERACTION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; X RAY ANALYSIS;

ALLOSTERIC REGULATION; ANTI-BACTERIAL AGENTS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN SYNTHESIS INHIBITORS; REPRESSOR PROTEINS; TETRACYCLINE; TETRACYCLINES;

EID: 33745140513     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm060289g     Document Type: Article

References (12)

1. Speer, B. S.; Shoemake, N. B.; Salyers, A. A. Bacterial Resistance to tetracycline: Mechanisms, transfer and clinical significance. Clin. Biol. Res. 1992, 5, 387-399.
2. Barza, M.; Schiefe, Richard T. Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 1: Tetracyclines. Am. J. Hosp. Pharm. 1977, 34, 49-57.
3. Saenger, W.; Orth, P.; Kisker, C.; Hillen, W.; Hinrichs, W. The Tetracycline Repressor - A Paradigm for a Biological Switch. Angew. Chem., Int. Ed. 2000, 39, 2042-2052
4. Hinrichs, W.; Kisker, C.; Duvel, M.; Muller, A.; Tovar, K.; Hillen, W.; Saenger, W. Structure of the Tet-repressor-tetracycline complex and regulation of antibiotic resistance. Science 1994, 264, 418-420.
5. Orth, P.; Saenger, W.; Hinrichs, W. Tetracycline-chelated Mg2+ ion initiates helix unwinding in Tet-repressor induction. Biochem., 1999, 38, 191-198.
6. Orth, P.; Schnappinger, D.; Sum, P.-E.; Ellestad, G. A.; Hillen, W.; Saenger, W.; Hinrichs, W., 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, 455-461.
7. 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, 215-219.
8. Lanig, H.; Othersen O. G.; Beierlein, F. R.; Seidel, U.; Clark, T. Molecular Dynamics Simulations of the Tetracycline-Repressor protein: The Mechanism of Induction. J. Mol. Biol. 2006, DOI, doi:10.1016/j.jmb.2006.04.014.
9. Cheatham, T. E., III. Ptraj 6.5. University of Utah, Salt Lake City, Utah, 2003.
10. The cavity surfaces and volumes were determined as outlined in the Supporting Information.
11. 2+. Biochemistry 2000, 39, 10914-10920.
12. Hinrichs, W.; Fenske, C. In Tetracyclines in Biology, Chemistry and Medicine; Nelson, M.; Hillen, W.; Greenwald, R. A.; Eds.; Birkhauser Verlag: Basel, Boston, Berlin, 2001; pp 107-123.