ornithine decarboxylase inhibitor activity / misfolded RNA binding / Group I intron splicing / RNA folding / four-way junction DNA binding / negative regulation of translational initiation / regulation of mRNA stability / mRNA regulatory element binding translation repressor activity / positive regulation of RNA splicing / DNA endonuclease activity ...ornithine decarboxylase inhibitor activity / misfolded RNA binding / Group I intron splicing / RNA folding / four-way junction DNA binding / negative regulation of translational initiation / regulation of mRNA stability / mRNA regulatory element binding translation repressor activity / positive regulation of RNA splicing / DNA endonuclease activity / transcription antitermination / DNA-templated transcription termination / maintenance of translational fidelity / mRNA 5'-UTR binding / regulation of translation / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / cytoplasmic translation / tRNA binding / rRNA binding / structural constituent of ribosome / ribosome / translation / response to antibiotic / zinc ion binding / cytosol / cytoplasm 類似検索 - 分子機能
Ribosomal protein S21, conserved site / Ribosomal protein S21 signature. / Ribosomal protein S21 superfamily / Ribosomal protein S21 / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein S21 / Ribosomal protein S6, conserved site / Ribosomal protein S6 signature. / Ribosomal protein S11, bacterial-type ...Ribosomal protein S21, conserved site / Ribosomal protein S21 signature. / Ribosomal protein S21 superfamily / Ribosomal protein S21 / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein S21 / Ribosomal protein S6, conserved site / Ribosomal protein S6 signature. / Ribosomal protein S11, bacterial-type / Ribosomal protein S20 / Ribosomal protein S20 superfamily / Ribosomal protein S20 / Ribosomal protein S4, bacterial-type / 30S ribosomal protein S17 / Ribosomal protein S5, bacterial-type / Ribosomal protein S6, plastid/chloroplast / Ribosomal protein S18, conserved site / Ribosomal protein S18 signature. / Ribosomal protein S16 / Ribosomal protein S16 domain superfamily / Ribosomal protein S16 / Ribosomal protein S15, bacterial-type / Ribosomal protein S6 / Ribosomal protein S6 / Ribosomal protein S6 superfamily / Ribosomal protein S12, bacterial-type / Translation elongation factor EF1B/ribosomal protein S6 / Ribosomal protein S18 / Ribosomal protein S18 / Ribosomal protein S18 superfamily / Ribosomal protein S5, N-terminal, conserved site / Ribosomal protein S5 signature. / : / Ribosomal protein S17, conserved site / Ribosomal protein S17 signature. / Ribosomal protein S5 / S5 double stranded RNA-binding domain profile. / Ribosomal protein S5, N-terminal / Ribosomal protein S5, C-terminal / Ribosomal protein S5, N-terminal domain / Ribosomal protein S5, C-terminal domain / Ribosomal protein S8 signature. / Ribosomal protein S4/S9 N-terminal domain / Ribosomal protein S4, conserved site / Ribosomal protein S15 signature. / Ribosomal protein S4 signature. / Ribosomal protein S4/S9 N-terminal domain / Ribosomal protein S4/S9, N-terminal / Ribosomal protein S4/S9 / Ribosomal protein S8 / Ribosomal protein S8 superfamily / Ribosomal protein S8 / S4 RNA-binding domain profile. / Ribosomal S11, conserved site / Ribosomal protein S11 signature. / S4 RNA-binding domain / S4 domain / RNA-binding S4 domain / Ribosomal protein S11 / RNA-binding S4 domain superfamily / Ribosomal protein S11 / Ribosomal protein S12 signature. / Ribosomal protein S12/S23 / Ribosomal protein S12/S23 / Ribosomal protein S17/S11 / Ribosomal protein S17 / Ribosomal protein S15 / Ribosomal_S15 / Ribosomal protein S15 / Ribosomal protein S11 superfamily / S15/NS1, RNA-binding / Ribosomal protein S5 domain 2-type fold, subgroup / Ribosomal protein S5 domain 2-type fold / Nucleic acid-binding, OB-fold 類似検索 - ドメイン・相同性
Small ribosomal subunit protein bS6 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein bS16 / Small ribosomal subunit protein bS18 / Small ribosomal subunit protein bS20 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS15 ...Small ribosomal subunit protein bS6 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein bS16 / Small ribosomal subunit protein bS18 / Small ribosomal subunit protein bS20 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Small ribosomal subunit protein bS21 類似検索 - 構成要素
ジャーナル: bioRxiv / 年: 2024 タイトル: A binding site for the antibiotic GE81112 in the ribosomal mRNA channel. 著者: Andreas Schedlbauer / Xu Han / Wouter van Bakel / Tatsuya Kaminishi / Borja Ochoa-Lizarralde / Idoia Iturrioz / Retina Çapuni / Ransford Parry / Ronny Zegarra / David Gil-Carton / Jorge P ...著者: Andreas Schedlbauer / Xu Han / Wouter van Bakel / Tatsuya Kaminishi / Borja Ochoa-Lizarralde / Idoia Iturrioz / Retina Çapuni / Ransford Parry / Ronny Zegarra / David Gil-Carton / Jorge P López-Alonso / Kristina Barragan Sanz / Letizia Brandi / Claudio O Gualerzi / Paola Fucini / Sean R Connell / 要旨: The initiation phase is the rate-limiting step of protein synthesis (translation) and is finely regulated, making it an important drug target. In bacteria, initiation is guided by three initiation ...The initiation phase is the rate-limiting step of protein synthesis (translation) and is finely regulated, making it an important drug target. In bacteria, initiation is guided by three initiation factors and involves positioning the start site on the messenger RNA within the P-site on the small ribosomal subunit (30S), where it is decoded by the initiator tRNA. This process can be efficiently inhibited by GE81112, a natural hydrophilic, noncyclic, nonribosomal tetrapeptide. It is found in nature in three structural variants (A, B and B1 with molecular masses of 643-658 Da). Previous biochemical and structural characterisation of GE81112 indicates that the primary mechanism of action of this antibiotic is to (1) prevent the initiator tRNA from binding correctly to the P-site and (2) block conformational rearrangements in initiation factor IF3, resulting in an 30S pre/C state. In this study, using cryoEM, we have determined the binding site of GE81112 in initiation complexes (3.2-3.7Å) and on empty ribosomes (2.09 Å). This binding site is within the mRNA channel (E-site) but remote from the binding site of the initiation factors and initiator tRNA. This suggests that it acts allosterically to prevent the initiator tRNA from being locked into place. The binding mode is consistent with previous biochemical studies and recent work identifying the key pharmacophores of GE81112.