7C7N

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

Summary for 7C7N

• Entry DOI: 10.2210/pdb7c7n/pdb
• Descriptor: DNA gyrase subunit B, 4-[[6-fluoranyl-8-(methylamino)-2-oxidanylidene-1~{H}-quinolin-3-yl]carbonylamino]benzoic acid (3 entities in total)
• Functional Keywords: inhibitor, complex, topoisomerase, escherichia coli, isomerase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 24546.50

Authors

Mima, M.,Ushiyama, F. (deposition date: 2020-05-26, release date: 2020-10-14, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)