11WQ

Schizosaccharomyces pombe acetyl-CoA synthetase

Summary for 11WQ

• Entry DOI: 10.2210/pdb11wq/pdb
• EMDB information: 76139
• Descriptor: Acetyl-coenzyme A synthetase (1 entity in total)
• Functional Keywords: acetyl-coa synthetase, ligase
• Biological source: Schizosaccharomyces pombe (fission yeast)
• Total number of polymer chains: 1
• Total formula weight: 74966.70

Authors

Li, M.,Zhou, M.,Marmorstein, R. (deposition date: 2026-03-16, release date: 2026-07-22, Last modification date: 2026-08-19)

Primary citation

Li, M.,Zhou, M.,Marmorstein, R.
Ligand-dependent interdomain rearrangements drive catalysis by acetyl-CoA synthetases.
Structure, 2026

PubMed Abstract: Acetyl-coenzyme A synthetases convert ATP, acetate, and coenzyme A (CoA) into acetyl-CoA, a central metabolite that fuels lipid biosynthesis and regulates protein and RNA acetylation. ACS enzymes contain N- and C-terminal domains that coordinate a two-step ping-pong mechanism involving sequential adenylation and thioester formation at the interdomain interface. How domain motions coordinate these chemical steps remains unclear. Here, we report single-particle cryo-electron microscopy structures of Schizosaccharomyces pombe ACSA captured in apo, pre-adenylation, intermediate, and product states. These structures reveal ligand-dependent reorganization of the C-terminal domain: apo and pre-adenylation forms display increased conformational heterogeneity, whereas intermediate- and product-bound states adopt ordered conformations compatible with catalysis. Structure-guided mutagenesis and in vitro activity assays, together with sequence conservation, support the functional importance and evolutionary conservation of the observed conformational transitions across ACS homologs. These findings establish a ligand-coupled interdomain rearrangement mechanism underlying catalysis by ACS enzymes and a structural framework for inhibitor development.

PubMed: 42567156
DOI: 10.1016/j.str.2026.07.009

Experimental method

ELECTRON MICROSCOPY (3.2 Å)