3JRW
Phosphorylated BC domain of ACC2
Summary for 3JRW
| Entry DOI | 10.2210/pdb3jrw/pdb |
| Related | 2HJW 3JRX |
| Descriptor | Acetyl-CoA carboxylase 2 (2 entities in total) |
| Functional Keywords | bc domain, phosphorylation, alternative splicing, atp-binding, biotin, fatty acid biosynthesis, ligase, lipid synthesis, manganese, membrane, metal-binding, multifunctional enzyme, nucleotide-binding, phosphoprotein, polymorphism |
| Biological source | Homo sapiens (human) |
| Cellular location | Endomembrane system: O00763 |
| Total number of polymer chains | 1 |
| Total formula weight | 65503.29 |
| Authors | |
| Primary citation | Cho, Y.S.,Lee, J.I.,Shin, D.,Kim, H.T.,Jung, H.Y.,Lee, T.G.,Kang, L.W.,Ahn, Y.J.,Cho, H.S.,Heo, Y.S. Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK Biochem.Biophys.Res.Commun., 391:187-192, 2010 Cited by PubMed Abstract: Acetyl-CoA carboxylases (ACCs) have been highlighted as therapeutic targets for obesity and diabetes, as they play crucial roles in fatty acid metabolism. ACC activity is regulated through the short-term mechanism of inactivation by reversible phosphorylation. Here, we report the crystal structures of the biotin carboxylase (BC) domain of human ACC2 phosphorylated by AMP-activated protein kinase (AMPK). The phosphorylated Ser222 binds to the putative dimer interface of BC, disrupting polymerization and providing the molecular mechanism of inactivation by AMPK. We also determined the structure of the human BC domain in complex with soraphen A, a macrocyclic polyketide natural product. This structure shows that the compound binds to the binding site of phosphorylated Ser222, implying that its inhibition mechanism is the same as that of phosphorylation by AMPK. PubMed: 19900410DOI: 10.1016/j.bbrc.2009.11.029 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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