3FF6

Human ACC2 CT domain with CP-640186

Summary for 3FF6

• Entry DOI: 10.2210/pdb3ff6/pdb
• Related: 1od2 1w2x
• Descriptor: Acetyl-CoA carboxylase 2, (3R)-1'-(9-ANTHRYLCARBONYL)-3-(MORPHOLIN-4-YLCARBONYL)-1,4'-BIPIPERIDINE (3 entities in total)
• Functional Keywords: acetyl coa carboxylase, acc2, acc, metabolic disorder, fatty acid metabolism, atp-binding, biotin, fatty acid biosynthesis, ligase, lipid synthesis, manganese, membrane, metal-binding, multifunctional enzyme, nucleotide-binding, phosphoprotein
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion : O00763
• Total number of polymer chains: 4
• Total formula weight: 346508.25

Authors

Williams, S.P.,Madauss, K.P.,Burkhart, W.A. (deposition date: 2008-12-02, release date: 2009-05-19, Last modification date: 2024-04-03)

Primary citation

Madauss, K.P.,Burkhart, W.A.,Consler, T.G.,Cowan, D.J.,Gottschalk, W.K.,Miller, A.B.,Short, S.A.,Tran, T.B.,Williams, S.P.
The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.
Acta Crystallogr.,Sect.D, 65:449-461, 2009

PubMed Abstract: Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target. Although the enzyme is highly conserved amongst animals, only the yeast enzyme structure is available for rational drug design. The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence. This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex. The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site. Differences in the observed inhibitor conformation between the yeast and human structures are caused by differing residues in the binding pocket.

PubMed: 19390150
DOI: 10.1107/S0907444909008014

Experimental method

X-RAY DIFFRACTION (3.19 Å)