7C7O

Crystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative

7C7O の概要

• エントリーDOI: 10.2210/pdb7c7o/pdb
• 分子名称: DNA gyrase subunit B, 4-[[4-(3-azanylpropylamino)-6-fluoranyl-8-(methylamino)-2-oxidanylidene-1~{H}-quinolin-3-yl]carbonylamino]benzoic acid (3 entities in total)
• 機能のキーワード: inhibitor, complex, topoisomerase, escherichia coli, isomerase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24618.61

構造登録者

Kamitani, M.,Mima, M.,Takeuchi, T.,Ushiyama, F. (登録日: 2020-05-26, 公開日: 2020-10-14, 最終更新日: 2023-11-29)

主引用文献

Ushiyama, F.,Amada, H.,Mihara, Y.,Takeuchi, T.,Tanaka-Yamamoto, N.,Mima, M.,Kamitani, M.,Wada, R.,Tamura, Y.,Endo, M.,Masuko, A.,Takata, I.,Hitaka, K.,Sugiyama, H.,Ohtake, N.
Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors.
Bioorg.Med.Chem., 28:115776-115776, 2020

PubMed Abstract: The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chemical class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 μg/mL, respectively. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chemical class.

PubMed: 33032189
DOI: 10.1016/j.bmc.2020.115776

実験手法

X-RAY DIFFRACTION (1.8 Å)