9QEA
CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM Mycobacterium tuberculosis COMPLEXED WITH L-LYSINE AND INHIBITOR DDD01839469
This is a non-PDB format compatible entry.
Summary for 9QEA
| Entry DOI | 10.2210/pdb9qea/pdb |
| Related | 9qbr 9qc3 9qc4 9qdj |
| Descriptor | Lysine--tRNA ligase 1, LYSINE, 2-azanyl-6-cyclohexyl-4-ethoxy-7~{H}-pyrrolo[3,4-d]pyrimidin-5-one, ... (4 entities in total) |
| Functional Keywords | ligase, inhibitor |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 1 |
| Total formula weight | 58613.22 |
| Authors | Dawson, A.,Cleghorn, L.A.T.,Davis, S.H. (deposition date: 2025-03-07, release date: 2025-08-13, Last modification date: 2025-08-27) |
| Primary citation | Davis, S.H.,Mathieson, M.,Buchanan, K.I.,Dawson, A.,Smith, A.,Cocco, M.,Tamaki, F.K.,Post, J.M.,Baragana, B.,Jansen, C.,Kiczun, M.,Zuccotto, F.,Wood, G.,Scullion, P.,Ray, P.C.,Epemolu, O.,Lopez-Roman, E.M.,Lopez, L.G.,Engelhart, C.A.,Kim, J.,Pino, P.A.,Schnappinger, D.,Read, K.D.,Encinas, L.,Bates, R.H.,Wyatt, P.G.,Green, S.R.,Cleghorn, L.A.T. Design and Development of Lysyl tRNA Synthetase Inhibitors, for the Treatment of Tuberculosis. J.Med.Chem., 68:16459-16482, 2025 Cited by PubMed Abstract: There is currently a public health crisis due to the rise of multidrug-resistant tuberculosis cases, as well as the rise in the number of deaths from tuberculosis. To achieve the United Nations Sustainable Development Goal of ending the tuberculosis epidemic by 2030, new treatments are urgently required. We previously reported the discovery of , a preclinical candidate that acted through inhibition of the lysyl tRNA synthetase (LysRS). In this report, the full medicinal chemistry program is reviewed from the original hit through to the optimized lead. The work was guided by the first crystal structures of LysRS. The physicochemical and pharmacokinetic properties were optimized to afford compounds suitable for evaluation in mouse efficacy models of tuberculosis and with the potential for clinical development. PubMed: 40749104DOI: 10.1021/acs.jmedchem.5c01331 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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