7ZTK

NME1 in complex with CoA

Summary for 7ZTK

• Entry DOI: 10.2210/pdb7ztk/pdb
• Related: 7ZL8 7ZLW
• Descriptor: Nucleoside diphosphate kinase A, COENZYME A (3 entities in total)
• Functional Keywords: nme1, complex, transferase, nucleoside diphosphate kinase 1, coenzyme-a
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 6
• Total formula weight: 109972.40

Authors

Garcia-Saez, I.,Iuso, D.,Khochbin, S.,Petosa, C. (deposition date: 2022-05-10, release date: 2023-08-09, Last modification date: 2023-09-20)

Primary citation

Iuso, D.,Garcia-Saez, I.,Coute, Y.,Yamaryo-Botte, Y.,Boeri Erba, E.,Adrait, A.,Zeaiter, N.,Tokarska-Schlattner, M.,Jilkova, Z.M.,Boussouar, F.,Barral, S.,Signor, L.,Couturier, K.,Hajmirza, A.,Chuffart, F.,Bourova-Flin, E.,Vitte, A.L.,Bargier, L.,Puthier, D.,Decaens, T.,Rousseaux, S.,Botte, C.,Schlattner, U.,Petosa, C.,Khochbin, S.
Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet.
Sci Adv, 9:eadh0140-eadh0140, 2023

PubMed Abstract: The synthesis of fatty acids from acetyl-coenzyme A (AcCoA) is deregulated in diverse pathologies, including cancer. Here, we report that fatty acid accumulation is negatively regulated by nucleoside diphosphate kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently found to bind CoA. We show that NME1 additionally binds AcCoA and that ligand recognition involves a unique binding mode dependent on the CoA/AcCoA 3' phosphate. We report that knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells, NME2 mediates a gene transcriptional response to HFD leading to the repression of fatty acid accumulation and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling AcCoA usage between the competing paths of histone acetylation and fatty acid synthesis.

PubMed: 37672589
DOI: 10.1126/sciadv.adh0140

Experimental method

X-RAY DIFFRACTION (2.6 Å)