Inositol Hexakisphosphate Is Bound in the ADAR2 Core and Required for RNA Editing

  • Mark R. Macbeth
    Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Heidi L. Schubert
    Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Andrew P. VanDemark
    Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Arunth T. Lingam
    Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Christopher P. Hill
    Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Brenda L. Bass
    Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.

書誌事項

公開日
2005-09-02
DOI
  • 10.1126/science.1113150
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:p> We report the crystal structure of the catalytic domain of human ADAR2, an RNA editing enzyme, at 1.7 angstrom resolution. The structure reveals a zinc ion in the active site and suggests how the substrate adenosine is recognized. Unexpectedly, inositol hexakisphosphate (IP <jats:sub>6</jats:sub> ) is buried within the enzyme core, contributing to the protein fold. Although there are no reports that adenosine deaminases that act on RNA (ADARs) require a cofactor, we show that IP <jats:sub>6</jats:sub> is required for activity. Amino acids that coordinate IP <jats:sub>6</jats:sub> in the crystal structure are conserved in some adenosine deaminases that act on transfer RNA (tRNA) (ADATs), related enzymes that edit tRNA. Indeed, IP <jats:sub>6</jats:sub> is also essential for in vivo and in vitro deamination of adenosine 37 of tRNA <jats:sup>ala</jats:sup> by ADAT1. </jats:p>

収録刊行物

  • Science

    Science 309 (5740), 1534-1539, 2005-09-02

    American Association for the Advancement of Science (AAAS)

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