Mechanism of Protein Synthesis Inhibition by Didemnin B in Vitro
| Autor: | Bhagyashri V. SirDeshpande, Peter L. Toogood |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Protein Synthesis Inhibitors
Depsipeptide Binding Sites Reticulocytes Chemistry Peptide Chain Elongation Translational Chromosomal translocation In Vitro Techniques RNA Transfer Amino Acyl Peptide Elongation Factors Peptides Cyclic Biochemistry Ribosome Didemnin B Peptidyltransferase activity Elongation factor Didemnin RNA Transfer Phe Peptide Elongation Factor 2 Depsipeptides Protein biosynthesis Animals Rabbits Ribosomes |
| Zdroj: | Biochemistry. 34:9177-9184 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi00028a030 |
| Popis: | The cytotoxic and immunosuppressive marine depsipeptide didemnin B is a potent inhibitor of protein biosynthesis in intact cells. Here, didemnin B is shown to inhibit protein synthesis in vitro during the elongation cycle, by preventing eukaryotic elongation factor 2-(eEF-2-) dependent translocation. No inhibition of aminoacyl-tRNA delivery or of peptidyltransferase activity is observed. Didemnin B stimulates eEF-1 alpha-dependent aminoacyl-tRNA binding to rabbit reticulocyte ribosomes, and eEF-1 alpha is required for inhibition of the subsequent translocation of phenylalanyl-tRNA(Phe) from the A- to the P-site. These observations suggest that didemnin B prevents translocation by stabilizing aminoacyl-tRNA bound to the ribosomal A-site, similar to the antibiotic kirromycin, and consistent with the known affinity of didemnins for elongation factor eEF-1 alpha [Crews et al. (1994) J. Biol. Chem. 269, 15411]. Unlike kirromycin, didemnin B does not prevent peptide bond formation, so inhibition is observed only at the translocation step. Inhibition of translocation by didemnin B is attenuated by increasing concentrations of eEF-2. |
| Databáze: | OpenAIRE |
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