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In silico study on the substrate binding manner in human myo-inositol monophosphatase 2

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Abstract

The human IMPA2 gene encoding myo-inositol monophosphatase 2 is highly implicated with bipolar disorder but the substrates and the reaction mechanism of myo-inositol monophosphatase 2 have not been well elucidated.9 In the present study, we constructed 3D models of three- and two-Mg2+-ion bound myo-inositol monophosphatase 2, and studied substrate-binding manners using the docking program AutoDock3. The subsequent study showed that the three-metal-ion model could interact with myo-inositol monophosphates, as follows: The phosphate moiety coordinated three Mg2+ ions, and the inositol ring formed hydrogen bonds with the amino acids conserved in the family. Furthermore, the OH group vicinal to the phosphate group formed a hydrogen bond with a non-bridging oxygen atom of the phosphate. These interactions have been proposed as crucial for forming the transitional state, bipyramidal structure in the bovine myo-inositol monophosphatase. We therefore propose that the human myo-inositol monophosphatase 2 interacts with myo-inositol monophosphates in the three-metal-ion bound form, and proceeds the dephosphorylation through the three-metal-ion theory.

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Acknowledgments

We thank Dr. E. Cooper at Ritusmeikan University for his helpful suggestions concerning the manuscript.

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Authors and Affiliations

  1. Laboratory of Pharmacoinformatics, School of Pharmacy, Ritusmeikan University, Kusatsu, Shiga, 525-8577, Japan

    Daisuke Furuta & Norihisa Fujita

  2. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan

    Tetsuo Ohnishi & Takeo Yoshikawa

  3. Department of Bioinformatics, College of Information Science and Engineering, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan

    Seisuke Fujita, Shujiro Okuda, Ryo Kobayashi, Satoshi Fukuno & Takeshi Kikuchi

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  1. Seisuke Fujita
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  2. Tetsuo Ohnishi
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  3. Shujiro Okuda
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  5. Satoshi Fukuno
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  9. Norihisa Fujita
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Correspondence to Norihisa Fujita.

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Fujita, S., Ohnishi, T., Okuda, S. et al. In silico study on the substrate binding manner in human myo-inositol monophosphatase 2. J Mol Model 17, 2559–2567 (2011). https://doi.org/10.1007/s00894-010-0937-8

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  • DOI: https://doi.org/10.1007/s00894-010-0937-8

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