Cyclic AMP Inhibits the Activity and Promotes the Acetylation of Acetyl-CoA Synthetase through Competitive Binding to the ATP/AMP Pocket
Publication in refereed journal

香港中文大學研究人員
替代計量分析
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其它資訊
摘要The high-affinity biosynthetic pathway for converting acetate to acetyl-coenzyme A (acetyl-CoA) is catalyzed by the central metabolic enzyme acetyl-coenzyme A synthetase (Acs), which is finely regulated both at the transcriptional level via cyclic AMP (cAMP)-driven trans-activation and at the post-translational level via acetylation inhibition. In this study, we discovered that cAMP directly binds to Salmonella enterica Acs (SeAcs) and inhibits its activity in a substrate-competitive manner. In addition, cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition. A crystal structure study and site-directed mutagenesis analyses confirmed that cAMP binds to the ATP/AMP pocket of SeAcs, and restrains SeAcs in an open conformation. The cAMP contact residues are well conserved from prokaryotes to eukaryotes, suggesting a general regulatory mechanism of cAMP on Acs.
著者Han, Shen, Wang, Cen, Wang, Wu, Li, Zhao, Zhang, Zhao
期刊名稱Journal of Biological Chemistry
出版年份2017
月份1
日期27
卷號292
期次4
出版社AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
頁次1374 - 1384
國際標準期刊號0021-9258
電子國際標準期刊號1083-351X
語言英式英語

上次更新時間 2020-20-11 於 02:36