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Curr Opin Microbiol. 2004 Apr;7(2):115-9.

A link between transcription and intermediary metabolism: a role for Sir2 in the control of acetyl-coenzyme A synthetase.

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Department of Bacteriology, University of Wisconsin-Madison, 264 Enzyme Institute, 1710 University Avenue, Madison, WI 53726-4087, USA.


The silent information regulator protein (Sir2) and its homologs (collectively known as sirtuins) are NAD+-dependent deacetylase enzymes involved in chromosome stability, gene silencing and cell aging in eukaryotes and archaea. The discovery that sirtuin-dependent protein deacetylation is a NAD+-consuming reaction established a link with the energy generation systems of the cell. This link to metabolism was recently extended to the post-translational control of the activity of short-chain fatty acyl-coenzyme A (adenosine monophosphate-forming) synthetases in bacteria and yeast. The crystal structure of the Sir protein complexed with a peptide of a protein substrate provided insights into how sirtuins interact with their protein substrates.

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