Crystal structure of a tandemly repeated PTP‐like myo ‐inositol hexa kis phosphatase (phytase)

Inositol phosphatases are involved in a variety of eukaryotic and prokaryotic cellular functions. Phytases are a phosphatase class that preferentially hydrolyze myo ‐inositol hexa kis phosphate (InsP 6 ) to lower phosphorylated myo ‐inositols. InsP 6 is the most abundant inositol phosphate in the cell and has been implicated in important cellular processes including DNA repair, mRNA export, cellular signaling, endocytosis and vesicular trafficking. The phytase expressed by Mitsuokella multacida (PhyAmm) is composed of tandemly repeated domains each possessing a protein tyrosine phosphatase active site signature sequence. Mutation of the N‐terminal catalytic cysteine (C250) to serine has no effect on the catalytic activity of the protein, whereas mutation of the equivalent residue in the C‐terminal domain (C548) completely inactivates the enzyme. These results indicate that despite the presence of all the catalytic residues, the N‐terminal domain of PhyAmm is inactive against InsP 6 . The crystal structure of PhyAmm was solved to further examine the role of the inactive domain. A comparison of the active and inactive domains has identified differences that may explain why the N‐terminal domain lacks catalytic activity, and suggests this domain may be capable of hydrolyzing lower phosphorylated myo ‐inositols. This work is supported by the Natural Sciences and Engineering Research Council of Canada and the Alberta Ingenuity Fund.