negative regulation of cytoplasmic translational initiation / misfolded RNA binding / Group I intron splicing / RNA folding / transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity ...negative regulation of cytoplasmic translational initiation / misfolded RNA binding / Group I intron splicing / RNA folding / transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of translational initiation / negative regulation of DNA-templated DNA replication initiation / mRNA regulatory element binding translation repressor activity / positive regulation of RNA splicing / ribosome assembly / transcription antitermination / translational initiation / DNA-templated transcription termination / response to radiation / maintenance of translational fidelity / mRNA 5'-UTR binding / large ribosomal subunit / transferase activity / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / small ribosomal subunit rRNA binding / ribosomal large subunit assembly / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / negative regulation of translation / rRNA binding / structural constituent of ribosome / ribosome / translation / ribonucleoprotein complex / response to antibiotic / negative regulation of DNA-templated transcription / mRNA binding / DNA binding / RNA binding / zinc ion binding / membrane / cytosol / cytoplasm 類似検索 - 分子機能
Ribosomal protein S21, conserved site / Ribosomal protein S21 signature. / Ribosomal protein L25, short-form / Ribosomal protein S14, bacterial/plastid / Ribosomal protein L31 type A / Ribosomal protein S21 superfamily / Ribosomal protein S21 / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein L31 signature. ...Ribosomal protein S21, conserved site / Ribosomal protein S21 signature. / Ribosomal protein L25, short-form / Ribosomal protein S14, bacterial/plastid / Ribosomal protein L31 type A / Ribosomal protein S21 superfamily / Ribosomal protein S21 / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein L31 signature. / Ribosomal protein S21 / Ribosomal protein L31 / Ribosomal protein L31 superfamily / Ribosomal protein L31 / Ribosomal protein L16 signature 1. / Ribosomal protein L21, conserved site / Ribosomal protein L21 signature. / Ribosomal protein L16 signature 2. / Ribosomal protein L16, conserved site / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / : / Ribosomal protein L17 signature. / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L36 signature. / Ribosomal protein L32p, bacterial type / 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 L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / Ribosomal protein L28 / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L18, bacterial-type / : / Ribosomal protein L6, bacterial-type / Ribosomal protein S19, bacterial-type / Ribosomal protein S3, bacterial-type / Ribosomal protein S13, bacterial-type / Ribosomal protein S6, conserved site / Ribosomal protein S6 signature. / Ribosomal protein S7, bacterial/organellar-type / Ribosomal protein S11, bacterial-type / Ribosomal protein L5, bacterial-type / Ribosomal protein S20 / Ribosomal protein S20 superfamily / Ribosomal protein S20 / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein S4, bacterial-type / Ribosomal protein L19, conserved site / Ribosomal protein L19 signature. / 30S ribosomal protein S17 / Ribosomal protein L27, conserved site / Ribosomal protein L27 signature. / Ribosomal protein S5, bacterial-type / Ribosomal protein S6, plastid/chloroplast / Ribosomal protein L20 signature. / Ribosomal protein L14P, bacterial-type / Ribosomal protein L34, conserved site / Ribosomal protein L34 signature. / Ribosomal protein S2, bacteria/mitochondria/plastid / Ribosomal protein L2, bacterial/organellar-type / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein L35 / Ribosomal protein L33 / Ribosomal protein L33 / Ribosomal protein L18 / Ribosomal L18 of archaea, bacteria, mitoch. and chloroplast / Ribosomal L28 family / Ribosomal protein L33 superfamily / Ribosomal protein S9, bacterial/plastid / Ribosomal protein L16 / Ribosomal protein L28/L24 / Ribosomal protein S18, conserved site / Ribosomal protein S18 signature. / Ribosomal protein L30, bacterial-type / Ribosomal protein S16 / Ribosomal protein S16 domain superfamily / Ribosomal protein S16 / L28p-like / Ribosomal protein S15, bacterial-type / Ribosomal protein S6 / Ribosomal protein S6 / Ribosomal protein L27 / Ribosomal L27 protein / Ribosomal protein S6 superfamily / Ribosomal protein L20 / Ribosomal protein S12, bacterial-type / Ribosomal L32p protein family / Ribosomal protein L19 / Ribosomal protein L19 / Ribosomal protein L20 / Ribosomal protein L20, C-terminal 類似検索 - ドメイン・相同性
Small ribosomal subunit protein bS18 / Large ribosomal subunit protein bL36 / Small ribosomal subunit protein bS21 / Large ribosomal subunit protein bL28 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS13 / Large ribosomal subunit protein bL20 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein bL34 ...Small ribosomal subunit protein bS18 / Large ribosomal subunit protein bL36 / Small ribosomal subunit protein bS21 / Large ribosomal subunit protein bL28 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS13 / Large ribosomal subunit protein bL20 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein bL34 / Large ribosomal subunit protein bL33 / Small ribosomal subunit protein uS10 / Large ribosomal subunit protein uL23 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein uL29 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein uL24 / Small ribosomal subunit protein uS8 / Large ribosomal subunit protein uL30 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein bS16 / Large ribosomal subunit protein bL32 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein bS20 / Small ribosomal subunit protein bS6 / Small ribosomal subunit protein uS7 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein bL19 / Large ribosomal subunit protein bL27 / Large ribosomal subunit protein bL31 / Large ribosomal subunit protein bL35 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein bL17 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein bL25 / Large ribosomal subunit protein bL21 類似検索 - 構成要素
ジャーナル: Sci Rep / 年: 2025 タイトル: Structure-function comparison of Arbekacin with other aminoglycosides elucidates its higher potency as bacterial translation inhibitor. 著者: Soneya Majumdar / Narayan Prasad Parajuli / Xueliang Ge / Suparna Sanyal / 要旨: Aminoglycoside antibiotics are well-known inhibitors of bacterial protein synthesis, which act mainly by inhibiting ribosomal translocation and inducing miscoding errors. Arbekacin (ABK) is a ...Aminoglycoside antibiotics are well-known inhibitors of bacterial protein synthesis, which act mainly by inhibiting ribosomal translocation and inducing miscoding errors. Arbekacin (ABK) is a semisynthetic aminoglycoside that was developed by adding a 3-amino-2-hydroxybutyric (AHB) moiety to the 2-deoxystreptamine (2-DOS) ring of dibekacin for counteracting the problem of enzyme-mediated resistance of aminoglycosides. Here, we have systematically compared the inhibition efficacy of ABK with other aminoglycosides by in vivo MIC determination and in vitro fast-kinetics based translocation and termination assays complemented with a high-resolution cryo-EM structure. ABK presents significantly lower MIC value compared to its parent antibiotics kanamycin and dibekacin. Consistent with that, ABK inhibits translocation with lower inhibition constant and reside on the ribosome for significantly longer time than the classical aminoglycosides. Our 3.1 Å resolution cryo-EM structure of ABK-bound ribosome containing mRNA and initiator-tRNA, shows interactions of the unique AHB moiety of ABK with rRNA nucleobases, which likely provide additional stabilization of ABK at the canonical aminoglycoside binding pocket and contribute to its prolonged dwelling time. Our structural and functional analyses provide molecular basis for higher potency of ABK in bacterial translation inhibition and opens the possibility of rational design of new antibiotics.