Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Thesis (Ph. D.)--Lund University.

Thesis (Ph. D.)--Lund University.

The role of calcium and the existence of calmodulin or other calcium-binding proteins in E. coli has received very little attention previously. In this study, it is demonstrated that growth and cell division of E. coli are very sensitive to a group of calmodulin antagonists. Mutants resistant to calmodulin inhibitors have been isolated. The fee mutants are resistant to 48/80, and are temperature sensitive for growth, involving some purtubation of the cell cycle. wseA mutants are resistant to at least two calmodulin antagonists, 48/80 and W-7, and produced a population of filamentous cells. Intensive studies with the feeBl mutant demonstrated that the mutation is located in the acceptor stem of tRNAleu3 which recognises the rare CUA codon. Other cloning studies have also shown that in all probability feeA is also a leucine tRNA gene, leul, which recognises the abundant codon, CUG. The specific base change in the feeAl mutant, however, remains to be identified. The feeBl mutant was shown to be impaired in the synthesis of B-galactosidase (which has 6 CUA codons in its mRNA), at both the permissive and non-permissive temperatures. It is proposed that the synthesis of other polypeptides requiring the translation of several CUA codons is severely reduced in feeB mutants at the restrictive temperature, and is reduced to a suboptimal level for function at the permissive temperature. It is further proposed that if such a polypeptide(s) regulates the level of a specific calcium-binding protein which is inhibited by 48/80, or in some other way affects the level of free intracellular Ca2+, this could lead to the observed resistance to the drug. In the case of feeA, it is difficult to explain the relationship between the mutation of an abundant tRNA and the observed drug resistance. Possible explanations for the action of a mutant tRNALeu1, including an effect upon the level or function of the rare tRNALeu3 are described in Chapter VIII.

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