| Structural highlights
7zta is a 10 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | Electron Microscopy, Resolution 2.7Å |
| Ligands: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
RS5_ECOLI With S4 and S12 plays an important role in translational accuracy. Many suppressors of streptomycin-dependent mutants of protein S12 are found in this protein, some but not all of which decrease translational accuracy (ram, ribosomal ambiguity mutations).[1] Located at the back of the 30S subunit body where it stabilizes the conformation of the head with respect to the body.[2] The physical location of this protein suggests it may also play a role in mRNA unwinding by the ribosome, possibly by forming part of a processivity clamp.[3]
Publication Abstract from PubMed
As antimicrobial resistance threatens our ability to treat common bacterial infections, new antibiotics with limited cross-resistance are urgently needed. In this regard, natural products that target the bacterial ribosome have the potential to be developed into potent drugs through structure-guided design, provided their mechanisms of action are well understood. Here we use inverse toeprinting coupled to next-generation sequencing to show that the aromatic polyketide tetracenomycin X primarily inhibits peptide bond formation between an incoming aminoacyl-tRNA and a terminal Gln-Lys (QK) motif in the nascent polypeptide. Using cryogenic electron microscopy, we reveal that translation inhibition at QK motifs occurs via an unusual mechanism involving sequestration of the 3' adenosine of peptidyl-tRNA(Lys) in the drug-occupied nascent polypeptide exit tunnel of the ribosome. Our study provides mechanistic insights into the mode of action of tetracenomycin X on the bacterial ribosome and suggests a path forward for the development of novel aromatic polyketide antibiotics.
Tetracenomycin X sequesters peptidyl-tRNA during translation of QK motifs.,Leroy EC, Perry TN, Renault TT, Innis CA Nat Chem Biol. 2023 Sep;19(9):1091-1096. doi: 10.1038/s41589-023-01343-0. Epub , 2023 Jun 15. PMID:37322159[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
- ↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
- ↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
- ↑ Leroy EC, Perry TN, Renault TT, Innis CA. Tetracenomycin X sequesters peptidyl-tRNA during translation of QK motifs. Nat Chem Biol. 2023 Sep;19(9):1091-1096. PMID:37322159 doi:10.1038/s41589-023-01343-0
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