2IBN

Crystal structure of Human myo-Inositol Oxygenase (MIOX)

Summary for 2IBN

• Entry DOI: 10.2210/pdb2ibn/pdb
• Descriptor: Inositol oxygenase, FE (III) ION, SULFATE ION, ... (6 entities in total)
• Functional Keywords: reductase, inositol, diiron, structural genomics, structural genomics consortium, sgc, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9UGB7
• Total number of polymer chains: 2
• Total formula weight: 60384.34

Authors

Hallberg, B.M.,Busam, R.D.,Arrowsmith, C.,Berglund, H.,Collins, R.,Edwards, A.,Ehn, M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Hogbom, M.,Holmberg-Schiavone, L.,Johansson, I.,Karlberg, T.,Kotenyova, T.,Nilsson-Ehle, P.,Nordlund, P.,Nyman, T.,Ogg, D.,Sagemark, J.,Stenmark, P.,Sundstrom, M.,Uppenberg, J.,Van Den Berg, S.,Weigelt, J.,Thorsell, A.G.,Persson, C.,Structural Genomics Consortium (SGC) (deposition date: 2006-09-11, release date: 2006-10-17, Last modification date: 2024-10-30)

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 (1.5 Å)