Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine
Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine
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DOI：
10.1126/science.1077650
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发表时间：
2002-12-20
期刊：
影响因子：
56.9
通讯作者：
Escalante-Semerena, JC
中科院分区：
文献类型：
--
作者：
Starai, VJ;Celic, I;Escalante-Semerena, JC
乙酰辅酶A（CoA）合成酶（Acs）是原核生物和真核生物中代谢的核心酶。Acs通过乙酰腺苷一磷酸（AMP）中间体从乙酸盐、三磷酸腺苷和CoA合成乙酰CoA。免疫印迹和质谱分析表明，肠道沙门氏菌Acs酶活性是由赖氨酸-609的乙酰化后调节。乙酰化阻断腺苷酸中间体的合成，但不影响酶的硫酯形成活性。乙酰化酶的激活需要来自S.肠我们建议，乙酰化调节所有的AMP形成家族的酶，包括非核糖体肽合成酶，荧光素酶，芳基和酰基辅酶A合成酶的活性。这些发现扩展了我们对Sir 2蛋白在基因沉默、染色体稳定性和细胞衰老中的作用的认识，并暗示赖氨酸乙酰化是真核生物和原核生物中常见的调控机制。
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.