7DOR

E. coli GyrB ATPase domain in complex with 4-nitropheno

7DOR の概要

• エントリーDOI: 10.2210/pdb7dor/pdb
• 分子名称: DNA gyrase subunit B, 1H-benzimidazol-2-amine, P-NITROPHENOL, ... (5 entities in total)
• 機能のキーワード: isomerase
• 由来する生物種: Escherichia coli K-12
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 45898.15

構造登録者

Yu, Y.,Zhou, H. (登録日: 2020-12-16, 公開日: 2021-10-27, 最終更新日: 2023-11-29)

主引用文献

Yu, Y.,Guo, J.,Cai, Z.,Ju, Y.,Xu, J.,Gu, Q.,Zhou, H.
Identification of new building blocks by fragment screening for discovering GyrB inhibitors.
Bioorg.Chem., 114:105040-105040, 2021

PubMed Abstract: DNA gyrase is an essential DNA topoisomerase that exists only in bacteria. Since novobiocin was withdrawn from the market, new scaffolds and new mechanistic GyrB inhibitors are urgently needed. In this study, we employed fragment screening and X-ray crystallography to identify new building blocks, as well as their binding mechanisms, to support the discovery of new GyrB inhibitors. In total, 84 of the 618 chemical fragments were shown to either thermally stabilize the ATPase domain of Escherichia coli GyrB or inhibit the ATPase activity of E. coli gyrase. Among them, the IC values of fragments 10 and 23 were determined to be 605.3 μM and 446.2 μM, respectively. Cocrystal structures of the GyrB ATPase domain with twelve fragment hits were successfully determined at a high resolution. All twelve fragments were deeply inserted in the pocket and formed H-bonds with Asp73 and Thr165, and six fragments formed an additional H-bond with the backbone oxygen of Val71. Fragment screening further highlighted the capability of Asp73, Thr165 and Val71 to bind chemicals and provided diverse building blocks for the design of GyrB inhibitors.

PubMed: 34098257
DOI: 10.1016/j.bioorg.2021.105040

実験手法

X-RAY DIFFRACTION (1.89 Å)