3BXD

Crystal structure of Mouse Myo-inositol oxygenase (re-refined)

3BXD の概要

• エントリーDOI: 10.2210/pdb3bxd/pdb
• 分子名称: INOSITOL OXYGENASE, FE (III) ION, HYDROXIDE ION, ... (6 entities in total)
• 機能のキーワード: protein-substrate complex, hd domain fold, diiron, oxidoreductase
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cytoplasm : Q9QXN5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33870.77

構造登録者

Hallberg, B.M. (登録日: 2008-01-13, 公開日: 2008-02-05, 最終更新日: 2023-08-30)

主引用文献

Thorsell, A.G.,Persson, C.,Voevodskaya, N.,Busam, R.D.,Hammarstrom, M.,Graslund, S.,Graslund, A.,Hallberg, B.M.
Structural and biophysical characterization of human myo-inositol oxygenase.
J.Biol.Chem., 283:15209-15216, 2008

PubMed Abstract: Altered inositol metabolism is implicated in a number of diabetic complications. The first committed step in mammalian inositol catabolism is performed by myo-inositol oxygenase (MIOX), which catalyzes a unique four-electron dioxygen-dependent ring cleavage of myo-inositol to D-glucuronate. Here, we present the crystal structure of human MIOX in complex with myo-inosose-1 bound in a terminal mode to the MIOX diiron cluster site. Furthermore, from biochemical and biophysical results from N-terminal deletion mutagenesis we show that the N terminus is important, through coordination of a set of loops covering the active site, in shielding the active site during catalysis. EPR spectroscopy of the unliganded enzyme displays a two-component spectrum that we can relate to an open and a closed active site conformation. Furthermore, based on site-directed mutagenesis in combination with biochemical and biophysical data, we propose a novel role for Lys(127) in governing access to the diiron cluster.

PubMed: 18364358
DOI: 10.1074/jbc.M800348200

実験手法

X-RAY DIFFRACTION (2 Å)