4CC6

Fragment-Based Discovery of 6 Azaindazoles As Inhibitors of Bacterial DNA Ligase

4CC6 の概要

• エントリーDOI: 10.2210/pdb4cc6/pdb
• 関連するPDBエントリー: 4CC5
• 分子名称: DNA LIGASE, SULFATE ION, 2-{[2-(1H-pyrazolo[3,4-c]pyridin-3-yl)-6-(trifluoromethyl)pyridin-4-yl]amino}ethanol, ... (4 entities in total)
• 機能のキーワード: ligase, liga, antibiotic design
• 由来する生物種: STAPHYLOCOCCUS AUREUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37144.13

構造登録者

Howard, S.,Amin, N.,Benowitz, A.B.,Chiarparin, E.,Cui, H.,Deng, X.,Heightman, T.D.,Holmes, D.J.,Hopkins, A.,Huang, J.,Jin, Q.,Kreatsoulas, C.,Martin, A.C.L.,Massey, F.,McCloskey, L.,Mortenson, P.N.,Pathuri, P.,Tisi, D.,Williams, P.A. (登録日: 2013-10-18, 公開日: 2014-06-18, 最終更新日: 2023-12-20)

主引用文献

Howard, S.,Amin, N.,Benowitz, A.B.,Chiarparin, E.,Cui, H.,Deng, X.,Heightman, T.D.,Holmes, D.J.,Hopkins, A.,Huang, J.,Jin, Q.,Kreatsoulas, C.,Martin, A.C.L.,Massey, F.,Mccloskey, L.,Mortenson, P.N.,Pathuri, P.,Tisi, D.,Williams, P.A.
Fragment-Based Discovery of 6-Azaindazoles as Inhibitors of Bacterial DNA Ligase.
Acs Med.Chem.Lett., 4:1208-, 2013

PubMed Abstract: Herein we describe the application of fragment-based drug design to bacterial DNA ligase. X-ray crystallography was used to guide structure-based optimization of a fragment-screening hit to give novel, nanomolar, AMP-competitive inhibitors. The lead compound 13 showed antibacterial activity across a range of pathogens. Data to demonstrate mode of action was provided using a strain of S. aureus, engineered to overexpress DNA ligase.

PubMed: 24900632
DOI: 10.1021/ML4003277

実験手法

X-RAY DIFFRACTION (2.01 Å)