Specific binding of divalent metal ions to tetracycline and to the Tet repressor/tetracycline complex.

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
Gottfried J PalmW Hinrichs

Abstract

Tetracyclines coordinate metal(II) ions under physiological conditions forming chelate complexes with their ketoenolate moiety at rings B and C. These metal(II) complexes are the biologically relevant molecules conferring the antibiotic character of the drug by inhibiting ribosomal protein biosynthesis in prokaryotes. The Tet repressor, TetR, is the molecular switch for tetracycline resistance determinants in gram-negative bacteria. TetR controls transcription of a gene encoding the integral membrane protein TetA, which mediates active efflux of a tetracycline-metal(II) cation, [MeTc](+), by equimolar antiport with a proton. We evaluated distinct characteristics of the metal binding by crystal structure determination of TetR/[MeTc](+) complexes and of association equilibrium constants of [MeTc](+) and TetR/[MeTc](+) complexes. Various divalent metal ions bind to the same octahedral coordination site, defined by a histidine side chain of TetR, the tetracycline, and three water molecules. Whereas association constants for [MeTc](+) vary within 3 orders of magnitude, association of the [MeTc](+) cation to TetR is very similar for all measured divalent metals. Taking intracellular cation concentrations into account, it is evident t...Continue Reading

References

Apr 15, 1979·Biochemical Pharmacology·C Coibion, P Laszlo
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Mar 20, 1966·Journal of the American Chemical Society·W A Baker, P M Brown
Jan 1, 1994·Annual Review of Microbiology·W Hillen, C Berens
Jun 27, 1998·Journal of Molecular Biology·P OrthW Hinrichs
Oct 26, 1999·Acta Crystallographica. Section D, Biological Crystallography·J W Pflugrath
May 24, 2003·Cold Spring Harbor Symposia on Quantitative Biology·A BashanA Yonath
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jul 19, 2006·Journal of Computational Chemistry·Alexey Aleksandrov, Thomas Simonson
Oct 24, 2006·Acta Crystallographica. Section D, Biological Crystallography·Susan E HeffronFrances Jurnak
Mar 17, 2007·Chembiochem : a European Journal of Chemical Biology·Alexey AleksandrovThomas Simonson
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Oct 1, 2009·Chemical Reviews·Zhen MaDavid P Giedroc
May 23, 2014·Journal of Molecular Modeling·Natércia F BrásMaria J Ramos
Jan 30, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ngo Thi Hai YenWinfried Hinrichs
Jun 29, 2010·Current Opinion in Structural Biology·Herschel Wade
Jan 28, 2012·Environmental Research·Christina S HölzelJohann Bauer
Mar 31, 2016·The FEBS Journal·Sebastiaan WertenWinfried Hinrichs
Oct 23, 2012·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Michael Lee BranhamPatrick Masina
Mar 10, 2010·Journal of Molecular Biology·Daniela DalmWinfried Hinrichs
Nov 18, 2009·Biophysical Journal·Alexey AleksandrovThomas Simonson
Nov 29, 2014·Biochemistry·Sebastiaan WertenWinfried Hinrichs
May 30, 2008·Diagnostic Microbiology and Infectious Disease·Cristina TanaseanuUNKNOWN 313 Study Group
Nov 9, 2016·Environmental Science and Pollution Research International·Charles W KnappAndrea Hinwood
Nov 29, 2011·Physical Chemistry Chemical Physics : PCCP·Benedetta CarlottiFausto Elisei
Oct 28, 2019·Scientific Reports·Fellipe A T de FigueiredoJoao Paulo M Issa
Sep 4, 2013·Acta Crystallographica. Section D, Biological Crystallography·Gesa VolkersWinfried Hinrichs
Oct 23, 2019·The Science of the Total Environment·Vito RizziPinalysa Cosma

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