4CC6
Fragment-Based Discovery of 6 Azaindazoles As Inhibitors of Bacterial DNA Ligase
Summary for 4CC6
Entry DOI | 10.2210/pdb4cc6/pdb |
Related | 4CC5 |
Descriptor | DNA LIGASE, SULFATE ION, 2-{[2-(1H-pyrazolo[3,4-c]pyridin-3-yl)-6-(trifluoromethyl)pyridin-4-yl]amino}ethanol, ... (4 entities in total) |
Functional Keywords | ligase, liga, antibiotic design |
Biological source | STAPHYLOCOCCUS AUREUS |
Total number of polymer chains | 1 |
Total formula weight | 37144.13 |
Authors | Howard, S.,Amin, N.,Benowitz, A.B.,Chiarparin, E.,Cui, H.,Deng, X.,Heightman, T.D.,Holmes, D.J.,Hopkins, A.,Huang, J.,Jin, Q.,Kreatsoulas, C.,Martin, A.C.L.,Massey, F.,McCloskey, L.,Mortenson, P.N.,Pathuri, P.,Tisi, D.,Williams, P.A. (deposition date: 2013-10-18, release date: 2014-06-18, Last modification date: 2023-12-20) |
Primary citation | Howard, S.,Amin, N.,Benowitz, A.B.,Chiarparin, E.,Cui, H.,Deng, X.,Heightman, T.D.,Holmes, D.J.,Hopkins, A.,Huang, J.,Jin, Q.,Kreatsoulas, C.,Martin, A.C.L.,Massey, F.,Mccloskey, L.,Mortenson, P.N.,Pathuri, P.,Tisi, D.,Williams, P.A. Fragment-Based Discovery of 6-Azaindazoles as Inhibitors of Bacterial DNA Ligase. Acs Med.Chem.Lett., 4:1208-, 2013 Cited by PubMed Abstract: Herein we describe the application of fragment-based drug design to bacterial DNA ligase. X-ray crystallography was used to guide structure-based optimization of a fragment-screening hit to give novel, nanomolar, AMP-competitive inhibitors. The lead compound 13 showed antibacterial activity across a range of pathogens. Data to demonstrate mode of action was provided using a strain of S. aureus, engineered to overexpress DNA ligase. PubMed: 24900632DOI: 10.1021/ML4003277 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.01 Å) |
Structure validation
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