4BUL

Novel hydroxyl tricyclics (e.g. GSK966587) as potent inhibitors of bacterial type IIA topoisomerases

4BUL の概要

• エントリーDOI: 10.2210/pdb4bul/pdb
• 分子名称: DNA GYRASE SUBUNIT B, DNA GYRASE SUBUNIT A, 5'-D(*TP*GP*TP*GP*CP*GP*GP*TP*GP*TP*AP*CP*CP*TP *AP*CP*GP*GP*CP*T)-3', 5'-D(*AP*GP*CP*CP*GP*TP*AP*GP*GP*TP*AP*CP*AP*CP *CP*GP*CP*AP*C)-3', ... (6 entities in total)
• 機能のキーワード: isomerase, type iia topoisomerases, nbtis
• 由来する生物種: STAPHYLOCOCCUS AUREUS; 詳細
• 細胞内の位置: Cytoplasm : Q99XG5
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 181445.11

構造登録者

Miles, T.J.,Hennessy, A.J.,Bax, B.,Brooks, G.,Brown, B.S.,Brown, P.,Cailleau, N.,Chen, D.,Dabbs, S.,Davies, D.T.,Esken, J.M.,Giordano, I.,Hoover, J.L.,Huang, J.,Jones, G.E.,Sukmar, S.K.K.,Spitzfaden, C.,Markwell, R.E.,Minthorn, E.A.,Rittenhouse, S.,Gwynn, M.N.,Pearson, N.D. (登録日: 2013-06-20, 公開日: 2013-08-07, 最終更新日: 2023-12-20)

主引用文献

Miles, T.J.,Hennessy, A.J.,Bax, B.,Brooks, G.,Brown, B.S.,Brown, P.,Cailleau, N.,Chen, D.,Dabbs, S.,Davies, D.T.,Esken, J.M.,Giordano, I.,Hoover, J.L.,Huang, J.,Jones, G.E.,Kusalakumari Sukmar, S.K.,Spitzfaden, C.,Markwell, R.E.,Minthorn, E.A.,Rittenhouse, S.,Gwynn, M.N.,Pearson, N.D.
Novel Hydroxyl Tricyclics (E.G., Gsk966587) as Potent Inhibitors of Bacterial Type Iia Topoisomerases.
Bioorg.Med.Chem.Lett., 23:5437-, 2013

PubMed Abstract: During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers.

PubMed: 23968823
DOI: 10.1016/J.BMCL.2013.07.013

実験手法

X-RAY DIFFRACTION (2.6 Å)