2ibn
Crystal structure of Human myo-Inositol Oxygenase (MIOX)Crystal structure of Human myo-Inositol Oxygenase (MIOX)
Structural highlights
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 PubMedAltered 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. Structural and biophysical characterization of human myo-inositol oxygenase.,Thorsell AG, Persson C, Voevodskaya N, Busam RD, Hammarstrom M, Graslund S, Graslund A, Hallberg BM J Biol Chem. 2008 May 30;283(22):15209-16. Epub 2008 Mar 24. PMID:18364358[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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OCA- Human
- Inositol oxygenase
- Arrowsmith, C
- Berg, S Van Den
- Berglund, H
- Busam, R D
- Collins, R
- Edwards, A
- Ehn, M
- Flodin, S
- Flores, A
- Graslund, S
- Hallberg, B M
- Hammarstrom, M
- Hogbom, M
- Holmberg-Schiavone, L
- Johansson, I
- Karlberg, T
- Kotenyova, T
- Nilsson-Ehle, P
- Nordlund, P
- Nyman, T
- Ogg, D
- Persson, C
- Structural genomic
- Sagemark, J
- Stenmark, P
- Sundstrom, M
- Thorsell, A G
- Uppenberg, J
- Weigelt, J
- Diiron
- Inositol
- Oxidoreductase
- Reductase
- Sgc