From a protein inhibitor of polyamine biosynthesis to a transcriptional regulatory factor

From a protein inhibitor of polyamine biosynthesis to a transcriptional regulatory factor

Antizyme long known to be a protein non-competitive inhibitor induced by polyamines the end product of the enzymic reaction of ornithine decarboxylase. Recently antizyme proved to be the atoC gene product encoding the response regulator of the bacterial twocomponent system AtoS-AtoC. The gene located just upstream of atoC encodes the sensor kinase named AtoS that modulates AtoC activity. In vitro phosphorylation of purified His10-tagged AtoC by AtoS a membrane protein in E. coli is affected by acetoacetate the inducer of expression of atoDAEB operon involving in the shortchain fatty acid metabolism. Antizyme is thus referred to as AtoC functioning both as a post-translational and transcriptional regulator. The AtoS-AtoC signal transduction system in E. coli has a positive regulatory role on poly-(R)-3-hydroxybutyrate biosynthesis. A number of polyamine analogues were synthesized and tested for their effects on the transcription of the above mentioned genes as well as for their ability to support growth of a polyamine-dependent E. coli strain. Deletion of the atoS-atoC locus results in diminished accumulation of cPHB compared to atoSCώ cells. Spermidine can induce the accumulation of cPHB in E. coli similarly to acetoacetate possessing a functional AtoS-AtoC TCS but not in cells lacking either or both components of this signal transduction system or in cells expressing AtoC with mutations in the phosphorylation site. Moreover the AtoC protein exhibited ATPase activity enhanced by AtoScatalysed phoshorylation as well as by specific oligonucleotide sequence containing the whole region for the cooperative binding to two adjacent sites of AtoC on the enhancer of atoDAEB operon. Based on the known three-dimensional structures of two-component regulatory systems a structural model of AtoC in complex with a proposed homodimeric domain of AtoS containing a putative phosphohistidine was constructed.

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National Hellenic Research Foundation (NHRF)

Helios - Repository of the National Hellenic Research Foundation (NHRF)

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Άλλες Συλλογές

English

2012-06-12T12:23:34Z

2007

2008-12-11T09:22:02Z

DOI: http://dx.doi.org/10.1007/s00726-007-0578-0

http://hdl.handle.net/10442/7936

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