9g79

From Proteopedia

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

Structural highlights

9g79 is a 2 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.89Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACSA_BACSU Catalyzes the conversion of acetate into acetyl-CoA (AcCoA), an essential intermediate at the junction of anabolic and catabolic pathways. AcsA undergoes a two-step reaction. In the first half reaction, AcsA combines acetate with ATP to form acetyl-adenylate (AcAMP) intermediate. In the second half reaction, it can then transfer the acetyl group from AcAMP to the sulfhydryl group of CoA, forming the product AcCoA (By similarity). Has a role in growth and sporulation on acetate.^[1]

Publication Abstract from PubMed

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.

Regulation of acetyl-CoA biosynthesis via an intertwined acetyl-CoA synthetase/acetyltransferase complex.,Zheng L, Du Y, Steinchen W, Girbig M, Abendroth F, Jalomo-Khayrova E, Bedrunka P, Bekeredjian-Ding I, Mais CN, Hochberg GKA, Freitag J, Bange G Nat Commun. 2025 Mar 15;16(1):2557. doi: 10.1038/s41467-025-57842-2. PMID:40089509^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Grundy FJ, Waters DA, Takova TY, Henkin TM. Identification of genes involved in utilization of acetate and acetoin in Bacillus subtilis. Mol Microbiol. 1993 Oct;10(2):259-71. PMID:7934817 doi:10.1111/j.1365-2958.1993.tb01952.x
↑ Zheng L, Du Y, Steinchen W, Girbig M, Abendroth F, Jalomo-Khayrova E, Bedrunka P, Bekeredjian-Ding I, Mais CN, Hochberg GKA, Freitag J, Bange G. Regulation of acetyl-CoA biosynthesis via an intertwined acetyl-CoA synthetase/acetyltransferase complex. Nat Commun. 2025 Mar 15;16(1):2557. PMID:40089509 doi:10.1038/s41467-025-57842-2