6QX2

3.4A structure of benzoisoxazole 3 with S.aureus DNA gyrase and DNA

Summary for 6QX2

• Entry DOI: 10.2210/pdb6qx2/pdb
• Related: 6QX1
• Descriptor: DNA gyrase subunit B,DNA gyrase subunit B, DNA (5'-D(*GP*AP*GP*CP*GP*TP*AP*CP*GP*GP*CP*CP*GP*TP*AP*CP*GP*CP*TP*T)-3'), (2~{R})-2-[[5-(2-chlorophenyl)-1,2-benzoxazol-3-yl]oxy]-2-phenyl-ethanamine, ... (13 entities in total)
• Functional Keywords: inhibitor, dna complex, isomerase
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 36
• Total formula weight: 993375.08

Authors

Bax, B.D. (deposition date: 2019-03-06, release date: 2019-04-17, Last modification date: 2024-11-13)

Primary citation

Thalji, R.K.,Raha, K.,Andreotti, D.,Checchia, A.,Cui, H.,Meneghelli, G.,Profeta, R.,Tonelli, F.,Tommasi, S.,Bakshi, T.,Donovan, B.T.,Howells, A.,Jain, S.,Nixon, C.,Quinque, G.,McCloskey, L.,Bax, B.D.,Neu, M.,Chan, P.F.,Stavenger, R.A.
Structure-guided design of antibacterials that allosterically inhibit DNA gyrase.
Bioorg.Med.Chem.Lett., 29:1407-1412, 2019

PubMed Abstract: A series of DNA gyrase inhibitors were designed based on the X-ray structure of a parent thiophene scaffold with the objective to improve biochemical and whole-cell antibacterial activity, while reducing cardiac ion channel activity. The binding mode and overall design hypothesis of one series was confirmed with a co-crystal structure with DNA gyrase. Although some analogs retained both biochemical activity and whole-cell antibacterial activity, we were unable to significantly improve the activity of the series and analogs retained activity against the cardiac ion channels, therefore we stopped optimization efforts.

PubMed: 30962087
DOI: 10.1016/j.bmcl.2019.03.029

Experimental method

X-RAY DIFFRACTION (3.4 Å)