4BUL

Novel hydroxyl tricyclics (e.g. GSK966587) as potent inhibitors of bacterial type IIA topoisomerases

Summary for 4BUL

• Entry DOI: 10.2210/pdb4bul/pdb
• Descriptor: DNA GYRASE SUBUNIT B, DNA GYRASE SUBUNIT A, 5'-D(*TP*GP*TP*GP*CP*GP*GP*TP*GP*TP*AP*CP*CP*TP *AP*CP*GP*GP*CP*T)-3', 5'-D(*AP*GP*CP*CP*GP*TP*AP*GP*GP*TP*AP*CP*AP*CP *CP*GP*CP*AP*C)-3', ... (6 entities in total)
• Functional Keywords: isomerase, type iia topoisomerases, nbtis
• Biological source: STAPHYLOCOCCUS AUREUS; More
• Cellular location: Cytoplasm : Q99XG5
• Total number of polymer chains: 6
• Total formula weight: 181445.11

Authors

Miles, T.J.,Hennessy, A.J.,Bax, B.,Brooks, G.,Brown, B.S.,Brown, P.,Cailleau, N.,Chen, D.,Dabbs, S.,Davies, D.T.,Esken, J.M.,Giordano, I.,Hoover, J.L.,Huang, J.,Jones, G.E.,Sukmar, S.K.K.,Spitzfaden, C.,Markwell, R.E.,Minthorn, E.A.,Rittenhouse, S.,Gwynn, M.N.,Pearson, N.D. (deposition date: 2013-06-20, release date: 2013-08-07, Last modification date: 2023-12-20)

Primary citation

Miles, T.J.,Hennessy, A.J.,Bax, B.,Brooks, G.,Brown, B.S.,Brown, P.,Cailleau, N.,Chen, D.,Dabbs, S.,Davies, D.T.,Esken, J.M.,Giordano, I.,Hoover, J.L.,Huang, J.,Jones, G.E.,Kusalakumari Sukmar, S.K.,Spitzfaden, C.,Markwell, R.E.,Minthorn, E.A.,Rittenhouse, S.,Gwynn, M.N.,Pearson, N.D.
Novel Hydroxyl Tricyclics (E.G., Gsk966587) as Potent Inhibitors of Bacterial Type Iia Topoisomerases.
Bioorg.Med.Chem.Lett., 23:5437-, 2013

PubMed Abstract: During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers.

PubMed: 23968823
DOI: 10.1016/J.BMCL.2013.07.013

Experimental method

X-RAY DIFFRACTION (2.6 Å)