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#translation inhibition

2 public questions tagged with this topic.

Eukaryotes gene regulation

Chloramphenicol inhibits:

Chloramphenicol binds domain V central loop of 23S rRNA in 50S subunit peptidyl transferase center overlapping A-site tRNA 3' end. Crystallography shows contacts with A2451, A2452, U2506 critical for aminoacyl positioning. Binding prevents proper orientation of incoming aminoacyl-tRNA inhibiting peptide bond formation arresting elongation. Low concentrations bacteriostatic, higher bactericidal. Mitochondrial ribosomes sensitive due to bacterial ancestry causing toxicity. Resistance conferred by cat gene encoding chloramphenicol acetyltransferase acetylating drug reducing ribosome affinity. Mechanism distinct from aminoglycosides affecting decoding or tetracyclines blocking A-site entry, exemplifying peptidyl transferase targeted inhibition selectively action on bacterial translation machinery effectively exploited therapeutically despite resistance concerns.

Ref: NCBI Bookshelf, Antibiotics: Chloramphenicol Inhibition of 50S Peptidyl Transferase Activity

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Eukaryotes gene regulation

Puromycin inhibits translation by:

Puromycin is aminonucleoside antibiotic mimicking 3' terminus of aminoacyl-tRNA with aromatic group linked via stable amide not labile ester. Puromycin enters ribosomal A-site accepting nascent polypeptide from P-site via peptidyl transferase, forming peptidyl-puromycin adduct that dissociates prematurely as truncated peptide bearing puromycin at C-terminus causing chain release independent of release factors. Resulting peptide targeted for degradation. At low concentrations used experimentally to label nascent chains and probe translation status, puromycin provides tool for polysome analysis. Resistance gene pac encoding N-acetyltransferase detoxifies antibiotic allowing selection of stable transformants expressing resistance widely used in mammalian cell engineering.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 6: Puromycin Mechanism – Premature Chain Termination

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