Klieber MA, Scholz O, Lochner S, Gmeiner P, Hillen W, Muller Y (2009)
Publication Type: Journal article, Original article
Publication year: 2009
Original Authors: Klieber M.A., Scholz O., Lochner S., Gmeiner P., Hillen W., Muller Y.A.
Publisher: Wiley-Blackwell
Book Volume: 276
Pages Range: 5610-5621
Journal Issue: 19
DOI: 10.1111/j.1742-4658.2009.07254.x
The bacterial tetracycline transcription regulation system mediated by the tetracycline repressor (TetR) is widely used to study gene expression in prokaryotes and eukaryotes. To study multiple genes in parallel, a triple mutant TetR(KLI) has been engineered that is selectively induced by the synthetic tetracycline derivative 4-de-dimethylamino-anhydrotetracycline (4-ddma-atc) and no longer by tetracycline, the inducer of wild-type TetR. In the present study, we report the crystal structure of TetR(KLI) in the absence and in complex with 4-ddma-atc at resolutions of 2.1 Å. Analysis of the structures in light of the available binding data and previously reported TetR complexes allows for a dissection of the origins of selectivity and specificity. In all crystal structures solved to date, the ligand-binding position, as well as the positioning of the residues lining the binding site, is extremely well conserved, irrespective of the chemical nature of the ligand. Selective recognition of 4-ddma-atc is achieved through fine-tuned hydrogen-bonding constraints introduced by the His64→Lys substitution, as well as a combination of hydrophobic effect and the removal of unfavorable electrostatic interactions through the introduction of Leu135 and Ile138. © 2009 FEBS.
APA:
Klieber, M.A., Scholz, O., Lochner, S., Gmeiner, P., Hillen, W., & Muller, Y. (2009). Structural origins for selectivity and specificity in an engineered bacterial repressor-inducer pair. Febs Journal, 276(19), 5610-5621. https://doi.org/10.1111/j.1742-4658.2009.07254.x
MLA:
Klieber, Michael A., et al. "Structural origins for selectivity and specificity in an engineered bacterial repressor-inducer pair." Febs Journal 276.19 (2009): 5610-5621.
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