Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine.
Acetyl-coenzyme A (CoA) synthetase (Acs) is an enzyme central to metabolism in prokaryotes and eukaryotes. Acs synthesizes acetyl CoA from acetate, adenosine triphosphate, and CoA through an acetyl-adenosine monophosphate (AMP) intermediate. Immunoblotting and mass spectrometry analysis showed that Salmonella enterica Acs enzyme activity is posttranslationally regulated by acetylation of lysine-609. Acetylation blocks synthesis of the adenylate intermediate but does not affect the thioester-forming activity of the enzyme. Activation of the acetylated enzyme requires the nicotinamide adenine dinucleotide-dependent protein deacetylase activity of the CobB Sir2 protein from S. enterica. We propose that acetylation modulates the activity of all the AMP-forming family of enzymes, including nonribosomal peptide synthetases, luciferase, and aryl- and acyl-CoA synthetases. These findings extend our knowledge of the roles of Sir2 proteins in gene silencing, chromosome stability, and cell aging and imply that lysine acetylation is a common regulatory mechanism in eukaryotes and prokaryotes.
Starai
V J
VJ
Department of Bacteriology, University of Wisconsin, Madison, WI 53706-1567, USA.
Celic
I
I
Cole
R N
RN
Boeke
J D
JD
Escalante-Semerena
J C
JC
D000106:Acetate-CoA Ligase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000107:Acetylation; D000214:Acyl Coenzyme A / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D003065:Coenzyme A / Q000378:metabolism; D017124:Conserved Sequence; D004789:Enzyme Activation; D015964:Gene Expression Regulation, Bacterial; D015151:Immunoblotting; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D009243:NAD / Q000378:metabolism; D010449:Peptide Mapping; D019779:Salmonella enterica / Q000201:enzymology* / Q000235:genetics; D037761:Sirtuins / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D009243:NAD; C009061:propionyl-coenzyme A; D000249:Adenosine Monophosphate; D037761:Sirtuins; D000106:Acetate-CoA Ligase; D008239:Lysine; D003065:Coenzyme A