3BXD

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

Summary for 3BXD

• Entry DOI: 10.2210/pdb3bxd/pdb
• Descriptor: INOSITOL OXYGENASE, FE (III) ION, HYDROXIDE ION, ... (6 entities in total)
• Functional Keywords: protein-substrate complex, hd domain fold, diiron, oxidoreductase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm : Q9QXN5
• Total number of polymer chains: 1
• Total formula weight: 33870.77

Authors

Hallberg, B.M. (deposition date: 2008-01-13, release date: 2008-02-05, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)