1KZN

Crystal Structure of E. coli 24kDa Domain in Complex with Clorobiocin

1KZN の概要

• エントリーDOI: 10.2210/pdb1kzn/pdb
• 分子名称: DNA GYRASE SUBUNIT B, CLOROBIOCIN (3 entities in total)
• 機能のキーワード: topoisomerase, gyrase b, clorobiocin, isomerase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm (Potential): P06982
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23288.50

構造登録者

Lafitte, D.,Lamour, V.,Tsvetkov, P.O.,Makarov, A.A.,Klich, M.,Deprez, P.,Moras, D.,Briand, C.,Gilli, R. (登録日: 2002-02-07, 公開日: 2002-06-19, 最終更新日: 2024-02-14)

主引用文献

Lafitte, D.,Lamour, V.,Tsvetkov, P.O.,Makarov, A.A.,Klich, M.,Deprez, P.,Moras, D.,Briand, C.,Gilli, R.
DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose.
Biochemistry, 41:7217-7223, 2002

PubMed Abstract: DNA gyrase is a major bacterial protein that is involved in replication and transcription and catalyzes the negative supercoiling of bacterial circular DNA. DNA gyrase is a known target for antibacterial agents since its blocking induces bacterial death. Quinolones, coumarins, and cyclothialidines have been designed to inhibit gyrase. Significant improvements can still be envisioned for a better coumarin-gyrase interaction. In this work, we obtained the crystal costructures of the natural coumarin clorobiocin and a synthetic analogue with the 24 kDa gyrase fragment. We used isothermal titration microcalorimetry and differential scanning calorimetry to obtain the thermodynamic parameters representative of the molecular interactions occurring during the binding process between coumarins and the 24 kDa gyrase fragment. We provide the first experimental evidence that clorobiocin binds gyrase with a stronger affinity than novobiocin. We also demonstrate the crucial role of both the hydroxybenzoate isopentenyl moiety and the 5'-alkyl group on the noviose of the coumarins in the binding affinity for gyrase.

PubMed: 12044152
DOI: 10.1021/bi0159837

実験手法

X-RAY DIFFRACTION (2.3 Å)