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Human ACC2 CT domain with CP-640186Human ACC2 CT domain with CP-640186
Structural highlights
Function[ACACB_HUMAN] ACC-beta may be involved in the provision of malonyl-CoA or in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInhibition 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. The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.,Madauss KP, Burkhart WA, Consler TG, Cowan DJ, Gottschalk WK, Miller AB, Short SA, Tran TB, Williams SP Acta Crystallogr D Biol Crystallogr. 2009 May;65(Pt 5):449-61. Epub 2009, Apr 18. PMID:19390150[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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