Journal Article

PUBDB-2024-05684

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule

Qin, C. ; Graf, L. G. ; Striska, K. ; Janetzky, M. ; Geist, N. ; Specht, R. ; Schulze, S. ; Palm, G.Extern*EMBL* ; Girbardt, B. ; Dörre, B. ; Berndt, L. ; Kemnitz, S. ; Doerr, M. ; Bornscheuer, U. T. ; Delcea, M. ; Lammers, M. (Corresponding author)Extern*EMBL*

2024
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-024-49952-0  doi:10.3204/PUBDB-2024-05684

Abstract: The AMP-forming acetyl-CoA synthetase is regulated by lysine acetylation both in bacteria and eukaryotes. However, the underlying mechanism is poorly understood. The Bacillus subtilis acetyltransferase AcuA and the AMP-forming acetyl-CoA synthetase AcsA form an AcuA•AcsA complex, dissociating upon lysine acetylation of AcsA by AcuA. Crystal structures of AcsA from Chloroflexota bacterium in the apo form and in complex with acetyl-adenosine-5′-monophosphate (acetyl-AMP) support the flexible C-terminal domain adopting different conformations. AlphaFold2 predictions suggest binding of AcuA stabilizes AcsA in an undescribed conformation. We show the AcuA•AcsA complex dissociates upon acetyl-coenzyme A (acetyl-CoA) dependent acetylation of AcsA by AcuA. We discover an intrinsic phosphotransacetylase activity enabling AcuA•AcsA generating acetyl-CoA from acetyl-phosphate (AcP) and coenzyme A (CoA) used by AcuA to acetylate and inactivate AcsA. Here, we provide mechanistic insights into the regulation of AMP-forming acetyl-CoA synthetases by lysine acetylation and discover an intrinsic phosphotransacetylase allowing modulation of its activity based on AcP and CoA levels.

Note: German Research Foundation grant No. LA2984-6/1 and LA2984-8/1 (DFG, Deutsche Forschungsgemeinschaft).

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2024

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