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2ibn
From Proteopedia
Crystal structure of Human myo-Inositol Oxygenase (MIOX)
Overview
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.
About this Structure
2IBN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Wed Jun 11 10:54:16 2008
Categories: Homo sapiens | Inositol oxygenase | Single protein | 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. | SGC, Structural Genomics Consortium. | Sagemark, J. | Stenmark, P. | Sundstrom, M. | Thorsell, A G. | Uppenberg, J. | Weigelt, J. | Diiron | Inositol | Oxidoreductase | Reductase | Sgc | Structural genomic | Structural genomics consortium
