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Inositol polyphosphate 1-phosphatase (1PTASE) and inositol monophosphatase
(MPTASE) are enzymes of the inositol signalling pathway that share similar
enzymatic activity [PMID:7761465]. Both enzymes exhibit an absolute requirement for
metal ions (Mg2+ is preferred), and both are uncompetitively inhibited by
submillimolar concentrations of Li+. Their amino acid sequences contain
a number of conserved motifs, which are also shared by several other
proteins related to MPTASE (including products of fungal QaX and qutG,
bacterial suhB and cysQ, and yeast hal2) [PMID:7761465].
Structural analysis of these proteins has revealed a common core of 155
residues: the core comprises 5 alpha-helices and 11 beta-strands, and
includes residues essential for metal binding and catalysis. While the
core has been conserved presumably to impart catalytic function, the
loops and regions of structure outside the core have evolved unique
regulatory domains [PMID:7761465].
An interesting property of the enzymes of this family is their sensitivity
to Li+ at levels achieved in patients undergoing therapy for manic
depression. The targets and mechanism of action of Li+ are unknown, but
overactive inositol phosphate signalling may account for symptoms of the
disease [PMID:2553271]. It has been proposed that these Li+-sensitive proteins
could represent targets for Li+ in manic depressive disease [PMID:7761465].
Recently, the fold of fructose 1,6-bisphosphatase (FBPTASE) was noted to
be identical to that of MPTASE [PMID:8382485]. FBPTASE is a critical enzyme in the
gluconeogenic pathway that removes the 1-phosphate from fructose 1,6-bis-
phosphate to form fructose 6-phosphate [PMID:2159755, PMID:3008716]. FBTASE also requires metal
ions for catalysis (Mg2+ and Mn2+ being preferred) and the enzyme is
potently inhibited by Li+.
1PTASE, MPTASE and FBPTASE share a sequence motif (Asp-Pro-Ile/Leu-Asp-
Gly/Ser-Thr/Ser) which has been shown to bind metal ions and participate
in catalysis. This motif is also found in the distantly-related fungal,
bacterial and yeast MPTASE homologues. It has been suggested that these
proteins define an ancient structurally conserved family involved in
diverse metabolic pathways, including inositol signalling, gluconeogenesis,
sulphate assimilation and possibly quinone metabolism [PMID:7761465].
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