9QEA

CRYSTAL STRUCTURE OF LYSYL-TRNA SYNTHETASE FROM Mycobacterium tuberculosis COMPLEXED WITH L-LYSINE AND INHIBITOR DDD01839469

これはPDB形式変換不可エントリーです。

9QEA の概要

• エントリーDOI: 10.2210/pdb9qea/pdb
• 関連するPDBエントリー: 9qbr 9qc3 9qc4 9qdj
• 分子名称: Lysine--tRNA ligase 1, LYSINE, 2-azanyl-6-cyclohexyl-4-ethoxy-7~{H}-pyrrolo[3,4-d]pyrimidin-5-one, ... (4 entities in total)
• 機能のキーワード: ligase, inhibitor
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58613.22

構造登録者

Dawson, A.,Cleghorn, L.A.T.,Davis, S.H. (登録日: 2025-03-07, 公開日: 2025-08-13, 最終更新日: 2025-08-27)

主引用文献

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

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: 40749104
DOI: 10.1021/acs.jmedchem.5c01331

実験手法

X-RAY DIFFRACTION (2.3 Å)