11WO
SpACSA with AMPCPP, conformation 1
Summary for 11WO
| Entry DOI | 10.2210/pdb11wo/pdb |
| EMDB information | 76137 |
| Descriptor | Acetyl-coenzyme A synthetase, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER (2 entities in total) |
| Functional Keywords | acetyl-coa synthetase, complex, ligase |
| Biological source | Schizosaccharomyces pombe (fission yeast) |
| Total number of polymer chains | 1 |
| Total formula weight | 75471.90 |
| 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 Cited by 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: 42567156DOI: 10.1016/j.str.2026.07.009 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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