2fj1
From Proteopedia
Crystal Structure Analysis of Tet Repressor (class D) in Complex with 7-Chlortetracycline-Nickel(II)
Structural highlights
FunctionTETR4_ECOLX TetR is the repressor of the tetracycline resistance element; its N-terminal region forms a helix-turn-helix structure and binds DNA. Binding of tetracycline to TetR reduces the repressor affinity for the tetracycline resistance gene (tetA) promoter operator sites. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTetracyclines 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. Specific binding of divalent metal ions to tetracycline and to the Tet repressor/tetracycline complex.,Palm GJ, Lederer T, Orth P, Saenger W, Takahashi M, Hillen W, Hinrichs W J Biol Inorg Chem. 2008 Jun 12;. PMID:18548290[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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