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PDBsum entry 4d7n
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Transcription
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PDB id
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4d7n
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References listed in PDB file
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Key reference
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Title
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Tetracycline repressor allostery does not depend on divalent metal recognition.
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Authors
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S.Werten,
D.Dalm,
G.J.Palm,
C.C.Grimm,
W.Hinrichs.
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Ref.
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Biochemistry, 2014,
53,
7990-7998.
[DOI no: ]
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PubMed id
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Abstract
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Genes that render bacteria resistant to tetracycline-derived antibiotics are
tightly regulated by repressors of the TetR family. In their physiologically
relevant, magnesium-complexed form, tetracyclines induce allosteric
rearrangements in the TetR homodimer, leading to its release from the promoter
and derepression of transcription. According to earlier crystallographic work,
recognition of the tetracycline-associated magnesium ion by TetR is crucial and
triggers the allosteric cascade. Nevertheless, the derivative
5a,6-anhydrotetracycline, which shows an increased affinity for TetR, causes
promoter release even in the absence of magnesium. To resolve this paradox, it
has been proposed that metal-free 5a,6-anhydrotetracycline acts via an
exceptional, conformationally different induction mode that circumvents the
normal magnesium requirement. We have tested this hypothesis by determining
crystal structures of TetR-5a,6-anhydrotetracycline complexes in the presence of
magnesium, ethylenediaminetetraacetic acid, or high concentrations of potassium.
Analysis of these three structures reveals that, irrespective of the metal, the
effects of 5a,6-anhydrotetracycline binding are indistinguishable from those of
canonical induction by other tetracyclines. Together with a close scrutiny of
the earlier evidence of a metal-triggered mechanism, these results demonstrate
that magnesium recognition per se is not a prerequisite for tetracycline
repressor allostery.
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