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Originally published In Press as doi:10.1074/jbc.M504863200 on May 17, 2005

J. Biol. Chem., Vol. 280, Issue 28, 26200-26205, July 15, 2005
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Residue Leu-641 of Acetyl-CoA Synthetase is Critical for the Acetylation of Residue Lys-609 by the Protein Acetyltransferase Enzyme of Salmonella enterica*

Vincent J. Starai{ddagger}, Jeffrey G. Gardner, and Jorge C. Escalante-Semerena§

From the Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53726-4087

Posttranslational regulation of protein function by acetylation is present throughout nature. Regulation of protein function by Sir2 protein (sirtuin) deacetylases is conserved in all domains of life. In the prokaryote Salmonella enterica, the metabolic enzyme acetyl-coenzyme A synthetase (Acs) is regulated by a Sir2-dependent protein acetylation/deacetylation system (SDPADS). The recent identification of the acetyltransferase enzyme responsible for the acetylation of Acs defined the SDPADS in prokaryotes. This report identifies one residue in Acs, Leu-641, which is critical for the acetylation of Acs by the protein acetyltransferase enzyme. In vivo and in vitro evidence shows that mutations at Leu-641 prevent the acetylation of Acs by protein acetyltransferase, maintain the Acs enzyme in its active state, and bypass the need for sirtuin deacetylase activity during growth on acetate.


Received for publication, May 3, 2005 , and in revised form, May 16, 2005.

* This work was supported in part by National Institutes of Health Grant GM62203 (to J. C. E.-S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} Supported by a Pfizer predoctoral fellowship and by the Jerome Stefaniak Fellowship awarded by the Dept. of Bacteriology/University of Wisconsin-Madison. Present address: Dept. of Biochemistry, Dartmouth Medical School, Hanover, NH 03755.

§ To whom correspondence should be addressed: 264 Enzyme Institute, 1710 University Ave., Madison, WI 53726-4087. Tel.: 608-262-7379; Fax: 608-265-7909; E-mail: escalante{at}bact.wisc.edu.


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