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Structural and Biophysical Characterization of Human myo-Inositol Oxygenase.

Structural and Biophysical Characterization of Human myo-Inositol Oxygenase. Research Abstract Details 

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  • Structural and Biophysical Characterization of Human myo-Inositol Oxygenase. Abstract Text:

    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.

    Structural and Biophysical Characterization of Human myo-Inositol Oxygenase. Publishing Authors By Initials

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    PUBMED ID PMID:

    MEDLINE DATE:

    Structural and Biophysical Characterization of Human myo-Inositol Oxygenase. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: The Journal of biological chemistry

    VOLUME: 283

    Page Numbers: 15209-16

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 24

    MONTH: 03

    YEAR: 2008

    Structural and Biophysical Characterization of Human myo-Inositol Oxygenase. Information

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    LANGUAGE: eng

    NlmUniqueID: 2985121

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    Grant and Affiliation Information for Structural and Biophysical Characterization of Human myo-Inositol Oxygenase.

    AFFILIATION: Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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