4LH7
Crystal structure of a LigA inhibitor
Summary for 4LH7
| Entry DOI | 10.2210/pdb4lh7/pdb |
| Related | 4LH6 |
| Descriptor | DNA ligase, 4-aminothieno[3,2-c]pyridine-2,7-dicarboxamide, BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | protein-inhibitor complex, ligase-ligase inhibitor complex, ligase/ligase inhibitor |
| Biological source | Enterococcus faecalis |
| Total number of polymer chains | 1 |
| Total formula weight | 37479.88 |
| Authors | Boriack-Sjodin, P.A.,Prince, D.B. (deposition date: 2013-06-30, release date: 2013-12-25, Last modification date: 2024-02-28) |
| Primary citation | Murphy-Benenato, K.,Wang, H.,McGuire, H.M.,Davis, H.E.,Gao, N.,Prince, D.B.,Jahic, H.,Stokes, S.S.,Boriack-Sjodin, P.A. Identification through structure-based methods of a bacterial NAD(+)-dependent DNA ligase inhibitor that avoids known resistance mutations. Bioorg.Med.Chem.Lett., 24:360-366, 2014 Cited by PubMed Abstract: In an attempt to identify novel inhibitors of NAD(+)-dependent DNA ligase (LigA) that are not affected by a known resistance mutation in the adenosine binding pocket, a detailed analysis of the binding sites of a variety of bacterial ligases was performed. This analysis revealed several similarities to the adenine binding region of kinases, which enabled a virtual screen of known kinase inhibitors. From this screen, a thienopyridine scaffold was identified that was shown to inhibit bacterial ligase. Further characterization through structure and enzymology revealed the compound was not affected by a previously disclosed resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent medicinal chemistry program identified substitutions that resulted in an inhibitor with moderate activity across various Gram-positive bacterial LigA enzymes. PubMed: 24287382DOI: 10.1016/j.bmcl.2013.11.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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