4D7M

TetR(D) in complex with anhydrotetracycline and magnesium

「2XPS」から置き換えられました

4D7M の概要

• エントリーDOI: 10.2210/pdb4d7m/pdb
• 関連するPDBエントリー: 4D7N
• 分子名称: TETRACYCLINE REPRESSOR PROTEIN CLASS D, 5A,6-ANHYDROTETRACYCLINE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: transcription, antibiotic resistance, tetr
• 由来する生物種: ESCHERICHIA COLI
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25022.21

構造登録者

Werten, S.,Dalm, D.,Palm, G.J.,Hinrichs, W. (登録日: 2014-11-25, 公開日: 2014-12-10, 最終更新日: 2023-12-20)

主引用文献

Werten, S.,Dalm, D.,Palm, G.J.,Grimm, C.C.,Hinrichs, W.
Tetracycline Repressor Allostery Does not Depend on Divalent Metal Recognition.
Biochemistry, 53:7990-, 2014

PubMed Abstract: 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.

PubMed: 25432019
DOI: 10.1021/BI5012805

実験手法

X-RAY DIFFRACTION (1.55 Å)