Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle

@article{Verschueren2019StructureOA,
  title={Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle},
  author={Koen H. G. Verschueren and Clement Blanchet and Jan Felix and Ann Dansercoer and Dirk E. De Vos and Yehudi Bloch and Jozef J. Van Beeumen and Dmitri I. Svergun and Irina Gutsche and Savvas N. Savvides and Kenneth Verstraete},
  journal={Nature},
  year={2019},
  volume={568},
  pages={571-575}
}
Across different kingdoms of life, ATP citrate lyase (ACLY, also known as ACL) catalyses the ATP-dependent and coenzyme A (CoA)-dependent conversion of citrate, a metabolic product of the Krebs cycle, to oxaloacetate and the high-energy biosynthetic precursor acetyl-CoA1. The latter fuels pivotal biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine2, and the acetylation of histones and proteins3,4. In autotrophic prokaryotes, ACLY is a hallmark enzyme of the… 
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Acly was expressed ubiquitously but was expressed particularly highly in tissues with high levels of lipogenesis, such as in the livers of mice fed a high-carbohydrate diet, and β-galactosidase staining was intense in the developing brain, in keeping with thehigh levels of de novo lipogenesis of the tissue.
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This is the first structure of any member of the acyl-CoA synthetase (NDP-forming) superfamily in complex with its organic acid substrate, and locating the citrate-binding site is significant for understanding the catalytic mechanism of each member, including the prototype SCS.
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