PMID- 18548290
OWN - NLM
STAT- MEDLINE
DCOM- 20090209
LR  - 20211020
IS  - 1432-1327 (Electronic)
IS  - 0949-8257 (Linking)
VI  - 13
IP  - 7
DP  - 2008 Sep
TI  - Specific binding of divalent metal ions to tetracycline and to the Tet 
      repressor/tetracycline complex.
PG  - 1097-110
LID - 10.1007/s00775-008-0395-2 [doi]
AB  - 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 that no other metal ion can compete with Mg(2+) for TetR/[MeTc](+) 
      complex formation.
FAU - Palm, Gottfried J
AU  - Palm GJ
AD  - Institut fur Biochemie, Universitat Greifswald, Felix-Hausdorff-Strasse 4, 17489, 
      Greifswald, Germany.
FAU - Lederer, Thomas
AU  - Lederer T
FAU - Orth, Peter
AU  - Orth P
FAU - Saenger, Wolfram
AU  - Saenger W
FAU - Takahashi, Masayuki
AU  - Takahashi M
FAU - Hillen, Wolfgang
AU  - Hillen W
FAU - Hinrichs, Winfried
AU  - Hinrichs W
LA  - eng
PT  - Journal Article
DEP - 20080612
PL  - Germany
TA  - J Biol Inorg Chem
JT  - Journal of biological inorganic chemistry : JBIC : a publication of the Society 
      of Biological Inorganic Chemistry
JID - 9616326
RN  - 0 (Metals)
RN  - 0 (Repressor Proteins)
RN  - 0 (tetracycline resistance-encoding transposon repressor protein)
RN  - F8VB5M810T (Tetracycline)
SB  - IM
MH  - Binding Sites
MH  - Metals/*chemistry
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Repressor Proteins/*chemistry
MH  - Spectrum Analysis, Raman
MH  - Substrate Specificity
MH  - Tetracycline/*chemistry
EDAT- 2008/06/13 09:00
MHDA- 2009/02/10 09:00
CRDT- 2008/06/13 09:00
PHST- 2007/12/20 00:00 [received]
PHST- 2008/05/28 00:00 [accepted]
PHST- 2008/06/13 09:00 [pubmed]
PHST- 2009/02/10 09:00 [medline]
PHST- 2008/06/13 09:00 [entrez]
AID - 10.1007/s00775-008-0395-2 [doi]
PST - ppublish
SO  - J Biol Inorg Chem. 2008 Sep;13(7):1097-110. doi: 10.1007/s00775-008-0395-2. Epub 
      2008 Jun 12.