TY - JOUR
T1 - Inhibition of protein synthesis in reticulocytes by antibiotics. V. Mechanism of action of pederine, an inhibitor of initiation and elongation
AU - Jacobs-Lorena, M.
AU - Brega, A.
AU - Baglioni, C.
N1 - Funding Information:
This work has been supported by grants of the National Science Foundation (GB-I4345) and of the National Institute of Health (HE 12691-02 ).
PY - 1971/6/30
Y1 - 1971/6/30
N2 - The mechanism of action of pederine, an inhibitor of protein synthesis extracted from the coleopter Paederus fuscipes, has been investigated. Polysome disaggregation takes place in intact cells incubated with low concentrations (10-20 ng/ml) of pederine. At higher concentrations protein synthesis is inhibited without concomitant run off of polysomes. Polysomes incubated in the presence of pederine are inactivated irreversibly. This has suggested that pederine binds to ribosomes. Puromycin releases only 50 % of the growing polypeptide chains in the presence of pederine. Moreover, pederine inhibits the formation of N-formyl-methionylpuromycin, which occurs when the reticulocyte cell free system is incubated with N-formyl-methionyl-tRNA in the presence of puromycin. These results have suggested that pederine may interfere with the translocation of both the initiator tRNA and peptidyl-tRNA from the aminoacyl to the peptidyl site. In addition, other ribosomal functions are probably affected by this drug. Polysome disaggregation caused by pederine results most likely from an imbalance between the rate of initiation and that of elongation. At low pederine concentrations initiation seems to be preferentially inhibited. After incubation with high levels of pederine polysomes are remarkably homogeneous in sedimentation behaviour.
AB - The mechanism of action of pederine, an inhibitor of protein synthesis extracted from the coleopter Paederus fuscipes, has been investigated. Polysome disaggregation takes place in intact cells incubated with low concentrations (10-20 ng/ml) of pederine. At higher concentrations protein synthesis is inhibited without concomitant run off of polysomes. Polysomes incubated in the presence of pederine are inactivated irreversibly. This has suggested that pederine binds to ribosomes. Puromycin releases only 50 % of the growing polypeptide chains in the presence of pederine. Moreover, pederine inhibits the formation of N-formyl-methionylpuromycin, which occurs when the reticulocyte cell free system is incubated with N-formyl-methionyl-tRNA in the presence of puromycin. These results have suggested that pederine may interfere with the translocation of both the initiator tRNA and peptidyl-tRNA from the aminoacyl to the peptidyl site. In addition, other ribosomal functions are probably affected by this drug. Polysome disaggregation caused by pederine results most likely from an imbalance between the rate of initiation and that of elongation. At low pederine concentrations initiation seems to be preferentially inhibited. After incubation with high levels of pederine polysomes are remarkably homogeneous in sedimentation behaviour.
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U2 - 10.1016/0005-2787(71)90665-4
DO - 10.1016/0005-2787(71)90665-4
M3 - Article
C2 - 5559977
AN - SCOPUS:0015245515
SN - 0005-2787
VL - 240
SP - 263
EP - 272
JO - BBA Section Nucleic Acids And Protein Synthesis
JF - BBA Section Nucleic Acids And Protein Synthesis
IS - 2
ER -