9G79

Cryo-EM structure of Acetyl-coenzyme A synthetase (AcsA) dimer

Summary for 9G79

• Entry DOI: 10.2210/pdb9g79/pdb
• EMDB information: 51116
• Descriptor: Acetyl-coenzyme A synthetase (1 entity in total)
• Functional Keywords: ac-coa synthetase acsa, acetate switch, gcn5-related n-acetyltransferase acua, biosynthetic protein
• Biological source: Bacillus subtilis
• Total number of polymer chains: 2
• Total formula weight: 129951.70

Authors

Zheng, L.J.,Du, Y.,Bange, G. (deposition date: 2024-07-20, release date: 2025-04-16)

Primary citation

Zheng, L.,Du, Y.,Steinchen, W.,Girbig, M.,Abendroth, F.,Jalomo-Khayrova, E.,Bedrunka, P.,Bekeredjian-Ding, I.,Mais, C.N.,Hochberg, G.K.A.,Freitag, J.,Bange, G.
Regulation of acetyl-CoA biosynthesis via an intertwined acetyl-CoA synthetase/acetyltransferase complex.
Nat Commun, 16:2557-2557, 2025

PubMed Abstract: Acetyl-CoA synthetase (Acs) generates acetyl-coenzyme A (Ac-CoA) but its excessive activity can deplete ATP and lead to a growth arrest. To prevent this, Acs is regulated through Ac-CoA-dependent feedback inhibition executed by Ac-CoA-dependent acetyltransferases such as AcuA in Bacillus subtilis. AcuA acetylates the catalytic lysine of AcsA turning the synthetase inactive. Here, we report that AcuA and AcsA form a tightly intertwined complex - the C-terminal domain binds to acetyltransferase domain of AcuA, while the C-terminus of AcuA occupies the CoA-binding site in the N-terminal domain of AcsA. Formation of the complex reduces AcsA activity in addition to the well-established acetylation of the catalytic lysine 549 in AcsA which we show can disrupt the complex. Thus, different modes of regulation accomplished through AcuA adjust AcsA activity to the concentrations of the different substrates of the reaction. In summary, our study provides detailed mechanistic insights into the regulatory framework underlying acetyl-CoA biosynthesis from acetate.

PubMed: 40089509
DOI: 10.1038/s41467-025-57842-2

Experimental method

ELECTRON MICROSCOPY (2.89 Å)