4CC5

Fragment-Based Discovery of 6 Azaindazoles As Inhibitors of Bacterial DNA Ligase

Summary for 4CC5

• Entry DOI: 10.2210/pdb4cc5/pdb
• Related: 4CC6
• Descriptor: DNA LIGASE, SULFATE ION, 2-chloranyl-6-(1H-1,2,4-triazol-3-yl)pyrazine, ... (4 entities in total)
• Functional Keywords: ligase, antibiotic design
• Biological source: STAPHYLOCOCCUS AUREUS
• Total number of polymer chains: 1
• Total formula weight: 37002.43

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

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: 24900632
DOI: 10.1021/ML4003277

Experimental method

X-RAY DIFFRACTION (1.88 Å)