Discovery of Allosteric Inhibition of Human ATP-Citrate Lyase

Carlotta Granchi

doi:10.1016/j.tips.2019.04.008

Discovery of Allosteric Inhibition of Human ATP-Citrate Lyase

Trends Pharmacol Sci. 2019 Jun;40(6):364-366. doi: 10.1016/j.tips.2019.04.008. Epub 2019 May 6.

Author

Carlotta Granchi¹

Affiliation

¹ Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy. Electronic address: carlotta.granchi@unipi.it.

PMID: 31072639
DOI: 10.1016/j.tips.2019.04.008

Abstract

ATP-citrate lyase (ACLY) is an enzyme that links glycolysis to lipid metabolism. To date only partial X-ray structures of ACLY have been solved, thus limiting the design of novel inhibitors. Wei and colleagues (published online in Nature April 3, 2019) now report the full structure of human ACLY in complex with NDI-091143, revealing an appealing allosteric inhibition mechanism for this compound.

Keywords: ACLY; X-ray structure; cryo-electron microscopy; inhibitor; sulfonamide.

Publication types

Comment

MeSH terms

ATP Citrate (pro-S)-Lyase*
Adenosine Triphosphate
Humans
Lipid Metabolism*
Multienzyme Complexes
Oxo-Acid-Lyases

Substances

Multienzyme Complexes
Adenosine Triphosphate
ATP Citrate (pro-S)-Lyase
Oxo-Acid-Lyases
citrate (pro-3S)-lyase