Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing.
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 (IP6) 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 IP6 is required for activity. Amino acids that coordinate IP6 in the crystal structure are conserved in some adenosine deaminases that act on transfer RNA (tRNA) (ADATs), related enzymes that edit tRNA. Indeed, IP6 is also essential for in vivo and in vitro deamination of adenosine 37 of tRNAala by ADAT1.
Macbeth
Mark R
MR
Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
Schubert
Heidi L
HL
Vandemark
Andrew P
AP
Lingam
Arunth T
AT
Hill
Christopher P
CP
Bass
Brenda L
BL
D000243:Adenosine Deaminase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010833:Phytic Acid / Q000737:chemistry / Q000378:metabolism*; D017393:RNA Editing; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins
D016601:RNA-Binding Proteins; D010833:Phytic Acid; D012343:RNA, Transfer; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase