| Autor: |
SirDeshpande BV; Willard H. Dow Laboratory, Department of Chemistry, University of Michigan, Ann Arbor 48109-1055, USA., Toogood PL |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemistry [Biochemistry] 1995 Jul 18; Vol. 34 (28), pp. 9177-84. |
| DOI: |
10.1021/bi00028a030 |
| Abstrakt: |
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: |
MEDLINE |
| Externí odkaz: |
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