7AZO の概要
| エントリーDOI | 10.2210/pdb7azo/pdb |
| 分子名称 | 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (62 entities in total) |
| 機能のキーワード | translation, rna, antibiotics, ribosome |
| 由来する生物種 | Thermus thermophilus HB8 詳細 |
| タンパク質・核酸の鎖数 | 111 |
| 化学式量合計 | 4723583.88 |
| 構造登録者 | |
| 主引用文献 | Zhang, J.,Lair, C.,Roubert, C.,Amaning, K.,Barrio, M.B.,Benedetti, Y.,Cui, Z.,Xing, Z.,Li, X.,Franzblau, S.G.,Baurin, N.,Bordon-Pallier, F.,Cantalloube, C.,Sans, S.,Silve, S.,Blanc, I.,Fraisse, L.,Rak, A.,Jenner, L.B.,Yusupova, G.,Yusupov, M.,Zhang, J.,Kaneko, T.,Yang, T.J.,Fotouhi, N.,Nuermberger, E.,Tyagi, S.,Betoudji, F.,Upton, A.,Sacchettini, J.C.,Lagrange, S. Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents. Cell, 186:1013-1025.e24, 2023 Cited by PubMed Abstract: The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classic macrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb. Structures of the ribosome with bound inhibitors were used to optimize sequanamycin to produce the advanced lead compound SEQ-9. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and it demonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results support further investigation of this series as TB clinical candidates, with the potential for use in new regimens against drug-susceptible and drug-resistant TB. PubMed: 36827973DOI: 10.1016/j.cell.2023.01.043 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (3.3 Å) |
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