large ribosomal subunit / small ribosomal subunit / 5S rRNA binding / transferase activity / ribosomal large subunit assembly / cytosolic large ribosomal subunit / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome ...large ribosomal subunit / small ribosomal subunit / 5S rRNA binding / transferase activity / ribosomal large subunit assembly / cytosolic large ribosomal subunit / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / zinc ion binding / metal ion binding / cytoplasm 類似検索 - 分子機能
Ribosomal protein L25, long-form / Ribosomal protein L25, beta domain / Ribosomal protein L25, C-terminal / Ribosomal protein TL5, C-terminal domain / : / Ribosomal protein S14, type Z / Ribosomal protein L31 type A / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein L31 signature. ...Ribosomal protein L25, long-form / Ribosomal protein L25, beta domain / Ribosomal protein L25, C-terminal / Ribosomal protein TL5, C-terminal domain / : / Ribosomal protein S14, type Z / Ribosomal protein L31 type A / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein L31 signature. / Ribosomal protein L31 / Ribosomal protein L31 superfamily / Ribosomal protein L31 / : / Ribosomal protein L16 signature 1. / : / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L9 signature. / Ribosomal protein L9, bacteria/chloroplast / Ribosomal protein L9, C-terminal / Ribosomal protein L9, C-terminal domain / Ribosomal protein L9, C-terminal domain superfamily / Ribosomal protein L17 signature. / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L36 signature. / Ribosomal protein L28/L24 superfamily / Ribosomal protein L25/Gln-tRNA synthetase, N-terminal / Ribosomal protein L25/Gln-tRNA synthetase, anti-codon-binding domain superfamily / Ribosomal protein L9, N-terminal domain superfamily / Ribosomal protein L9 / Ribosomal protein L9, N-terminal / Ribosomal protein L9, N-terminal domain / : / : / Ribosomal protein L28 / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / Ribosomal protein L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L5, bacterial-type / Ribosomal protein L18, bacterial-type / Ribosomal protein L6, bacterial-type / Ribosomal protein S14/S29 / Ribosomal protein L9/RNase H1, N-terminal / Ribosomal protein L19, conserved site / Ribosomal protein L19 signature. / Ribosomal protein S3, bacterial-type / Ribosomal protein S6, conserved site / Ribosomal protein S6 signature. / Ribosomal protein S19, bacterial-type / Ribosomal protein S13, bacterial-type / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein S7, bacterial/organellar-type / Ribosomal protein S11, bacterial-type / Ribosomal protein S20 / Ribosomal protein S20 superfamily / Ribosomal protein S20 / Ribosomal protein L20 signature. / Ribosomal protein S9, bacterial/plastid / Ribosomal protein L27, conserved site / Ribosomal protein L27 signature. / Ribosomal protein S4, bacterial-type / 30S ribosomal protein S17 / Ribosomal protein S5, bacterial-type / Ribosomal protein L14P, bacterial-type / Ribosomal protein S6, plastid/chloroplast / Ribosomal protein L22, bacterial/chloroplast-type / Ribosomal protein L2, bacterial/organellar-type / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein L35 / Ribosomal protein L34, conserved site / Ribosomal L28 family / Ribosomal protein L34 signature. / Ribosomal protein L33 / Ribosomal protein L33 / Ribosomal protein L28/L24 / Ribosomal protein L18 / Ribosomal L18 of archaea, bacteria, mitoch. and chloroplast / Ribosomal protein L33 superfamily / Ribosomal protein L30, bacterial-type / Ribosomal protein S18, conserved site / Ribosomal protein S18 signature. / Ribosomal protein L16 / Ribosomal protein S16 / Ribosomal protein S16 domain superfamily / Ribosomal protein S16 / : / L28p-like / Ribosomal protein L20 / Ribosomal protein S15, bacterial-type / Ribosomal protein L20 / Ribosomal protein L20, C-terminal 類似検索 - ドメイン・相同性
Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein bS20 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein bL31 / Small ribosomal subunit protein uS10 / Large ribosomal subunit protein uL14 ...Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein bS20 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein bL31 / Small ribosomal subunit protein uS10 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein bL33 / Small ribosomal subunit protein uS14 / Large ribosomal subunit protein uL5 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS9 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein bL19 / Large ribosomal subunit protein bL32 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein bL17 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS8 / Large ribosomal subunit protein uL15 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein bL25 / Small ribosomal subunit protein bS16 / Small ribosomal subunit protein uS15 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein uL18 / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein bS6 / Small ribosomal subunit protein bS18 / Large ribosomal subunit protein bL9 / Large ribosomal subunit protein bL27 / Large ribosomal subunit protein bL20 / Large ribosomal subunit protein bL35 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein uL13 / 30S ribosomal protein THX / 50S ribosomal protein L36 / 50S ribosomal protein L34 / : / Small ribosomal subunit protein uS12 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P01AI095208
米国
Welch Foundation
A1863
米国
引用
ジャーナル: Cell / 年: 2023 タイトル: Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents. 著者: Jidong Zhang / Christine Lair / Christine Roubert / Kwame Amaning / María Belén Barrio / Yannick Benedetti / Zhicheng Cui / Zhongliang Xing / Xiaojun Li / Scott G Franzblau / Nicolas Baurin ...著者: Jidong Zhang / Christine Lair / Christine Roubert / Kwame Amaning / María Belén Barrio / Yannick Benedetti / Zhicheng Cui / Zhongliang Xing / Xiaojun Li / Scott G Franzblau / Nicolas Baurin / Florence Bordon-Pallier / Cathy Cantalloube / Stephanie Sans / Sandra Silve / Isabelle Blanc / Laurent Fraisse / Alexey Rak / Lasse B Jenner / Gulnara Yusupova / Marat Yusupov / Junjie Zhang / Takushi Kaneko / T J Yang / Nader Fotouhi / Eric Nuermberger / Sandeep Tyagi / Fabrice Betoudji / Anna Upton / James C Sacchettini / Sophie Lagrange / 要旨: 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 ...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.