4EMV

Crystal structure of a topoisomerase ATP inhibitor

4EMV の概要

• エントリーDOI: 10.2210/pdb4emv/pdb
• 関連するPDBエントリー: 4EM7
• 分子名称: DNA topoisomerase IV, B subunit, 5-{2-(ethylcarbamoyl)-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}pyridine-3-carboxylic acid (3 entities in total)
• 機能のキーワード: protein-inhibitor complex, atp binding, structure-based drug design, antimicrobial, virtual screen, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• 由来する生物種: Streptococcus pneumoniae GA47373
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25045.09

構造登録者

Boriack-Sjodin, P.A.,Manchester, J.,Hull, K. (登録日: 2012-04-12, 公開日: 2012-08-01, 最終更新日: 2024-02-28)

主引用文献

Manchester, J.I.,Dussault, D.D.,Rose, J.A.,Boriack-Sjodin, P.A.,Uria-Nickelsen, M.,Ioannidis, G.,Bist, S.,Fleming, P.,Hull, K.G.
Discovery of a novel azaindole class of antibacterial agents targeting the ATPase domains of DNA gyrase and Topoisomerase IV.
Bioorg.Med.Chem.Lett., 22:5150-5156, 2012

PubMed Abstract: We present the discovery and optimization of a novel series of bacterial topoisomerase inhibitors. Starting from a virtual screening hit, activity was optimized through a combination of structure-based design and physical property optimization. Synthesis of fewer than a dozen compounds was required to achieve inhibition of the growth of methicillin-resistant Staphyloccus aureus (MRSA) at compound concentrations of 1.56 μM. These compounds simultaneously inhibit DNA gyrase and Topoisomerase IV at similar nanomolar concentrations, reducing the likelihood of the spontaneous occurrence of target-based mutations resulting in antibiotic resistance, an increasing threat in the treatment of serious infections.

PubMed: 22814212
DOI: 10.1016/j.bmcl.2012.05.128

実験手法

X-RAY DIFFRACTION (1.7 Å)