2vpr | pdb_00002vpr

Tet repressor class H in complex with 5a,6- anhydrotetracycline-Mg

spinqualitylabelsall models 2vpr, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vpr is a 1 chain structure with sequence from "bacterium_multocidum"_lehmann_and_neumann_1899 "bacterium multocidum" lehmann and neumann 1899. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, SO4, TDC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 PubMed The Tet repressor (TetR) mediates the most important mechanism of bacterial resistance against tetracycline (Tc) antibiotics. In the absence of Tc, TetR is tightly bound to its operator DNA; upon binding of Tc with an associated Mg(2+) ion, it dissociates from the DNA, allowing expression of the repressed genes. Its tight control by Tc makes TetR broadly useful in genetic engineering. The Tc binding site is over 20 A from the DNA, so the binding signal must propagate a long distance. We use molecular dynamics simulations and continuum electrostatic calculations to test two models of the allosteric mechanism. We simulate the TetR:DNA complex, the Tc-bound, "induced" TetR, and the transition pathway between them. The simulations support the model inferred previously from the crystal structures and reveal new details. When [Tc:Mg](+) binds, the Mg(2+) ion makes direct and water-mediated interactions with helix 8 of one TetR monomer and helix 6 of the other monomer, and helix 6 is pulled in towards the central core of the structure. Hydrophobic interactions with helix 6 then pull helix 4 in a pendulum motion, with a maximal displacement at its N-terminus: the DNA interface. The crystal structure of an additional TetR reported here corroborates this motion. The N-terminal residue of helix 4, Lys48, is highly conserved in DNA-binding regulatory proteins of the TetR class and makes the largest contribution of any amino acid to the TetR:DNA binding free energy. Thus, the conformational changes lead to a drastic reduction in the TetR:DNA binding affinity, allowing TetR to detach itself from the DNA. Tc plays the role of a specific Mg(2+) carrier, whereas the Mg(2+) ion itself makes key interactions that trigger the allosteric transition in the TetR:Tc complex. Tet repressor induction by tetracycline: a molecular dynamics, continuum electrostatics, and crystallographic study.,Aleksandrov A, Schuldt L, Hinrichs W, Simonson T J Mol Biol. 2008 May 9;378(4):898-912. Epub 2008 Mar 19. PMID:18395746 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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