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EMBO Rep. 2012 Sep;13(9):835-9. doi: 10.1038/embor.2012.106. Epub 2012 Jul 20.

Positive allosteric feedback regulation of the stringent response enzyme RelA by its product.

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  • 1Biomedical Technology, Institute of Technology, University of Tartu, Nooruse 1, Tartu 51017, Estonia.


During the stringent response, Escherichia coli enzyme RelA produces the ppGpp alarmone, which in turn regulates transcription, translation and replication. We show that ppGpp dramatically increases the turnover rate of its own ribosome-dependent synthesis by RelA, resulting in direct positive regulation of an enzyme by its product. Positive allosteric regulation therefore constitutes a new mechanism of enzyme activation. By integrating the output of individual RelA molecules and ppGpp degradation pathways, this regulatory circuit contributes to a fast and coordinated transition to stringency.

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