8RPK

AMP-forming Acetyl-CoA synthetase from Chloroflexota bacterium without bound ligand

Summary for 8RPK

• Entry DOI: 10.2210/pdb8rpk/pdb
• Descriptor: Acetate--CoA ligase, MAGNESIUM ION, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: acsa, coa, phospho histidine, ligase
• Biological source: Chloroflexota bacterium
• Total number of polymer chains: 4
• Total formula weight: 296602.38

Authors

Striska, K.,Palm, G.J.,Lammers, M. (deposition date: 2024-01-16, release date: 2024-06-19, Last modification date: 2024-07-31)

Primary citation

Qin, C.,Graf, L.G.,Striska, K.,Janetzky, M.,Geist, N.,Specht, R.,Schulze, S.,Palm, G.J.,Girbardt, B.,Dorre, B.,Berndt, L.,Kemnitz, S.,Doerr, M.,Bornscheuer, U.T.,Delcea, M.,Lammers, M.
Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule.
Nat Commun, 15:6002-6002, 2024

PubMed 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.

PubMed: 39019872
DOI: 10.1038/s41467-024-49952-0

Experimental method

X-RAY DIFFRACTION (2.615 Å)