Combined Biophysical and Biochemical Study of Enzyme Effects: Binding Mechanism of an Inhibitor Febuxostat with Xanthine Oxidoreductase

DOI IR Web Site Web Site 10 References
  • Fujisaki Hiroshi
    Department of Physics, Nippon Medical School Computational Science Research Program, RIKEN
  • Furuta Tadaomi
    Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology
  • Okamoto Ken
    Department of Biochemistry, Nippon Medical School
  • Kikuchi Hiroto
    Department of Physics, Nippon Medical School

Bibliographic Information

Other Title
  • 理論生物物理と生化学を組み合わせた薬効研究　キサンチン酸化還元酵素と阻害剤フェブキソスタットの結合機序
  • 基礎科学から医学・医療を見る 理論生物物理と生化学を組み合わせた薬効研究 : キサンチン酸化還元酵素と阻害剤フェブキソスタットの結合機序
  • キソ カガク カラ イガク ・ イリョウ オ ミル リロン セイブツ ブツリ ト セイカガク オ クミアワセタ ヤッコウ ケンキュウ : キサンチン サンカ カンゲン コウソ ト ソガイザイ フェブキソスタット ノ ケツゴウ キジョ

Search this article

Abstract

We review our recent collaborative study, performed by computational physicists and biochemists, of the enzyme effects due to the drug called febuxostat. Febuxostat, which was recently approved in the US, European Union and Japan for treatment of gout, inhibits xanthine oxidoreductase (XOR)-mediated generation of uric acid during purine catabolism. Experiments have shown that febuxostat has strong effects on mammalian XOR but not on bacterial XOR, although the two enzymes have similar three-dimensional structures. To clarify the difference in the inhibitory power of febuxostat, we performed docking and molecular dynamics simulations for mammalian and bacterial XORs. We found that the static structures are not sufficient to explain the binding difference and that important interactions occur between febuxostat and the active region of the enzymes which suggests a better strategy for drug design.<br>

Journal

References(10)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top