TY - JOUR
T1 - The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate. Overlapping substrate specificities in a Mutt-type protein phosphohydrolase
AU - Safrany, Stephen T.
AU - Ingram, Stephen W.
AU - Cartwright, Jared L.
AU - Falck, J. R.
AU - McLennan, Alexander G.
AU - Barnes, Larry D.
AU - Shears, Stephen B.
PY - 1999/7/30
Y1 - 1999/7/30
N2 - Aps1 from Schizosaccharomyces pombe (Ingram, S. W., Stratemann, S. A., and Barnes, L. D. (1999) Biochemistry 38, 3649-3655) and YOR163w from Saccharomyces cerevisiae (Cartwright, J. L., and McLennan, A. G. (1999) J. Biol. Chem. 274, 8604-8610) have both previously been characterized as Mutt family hydrolases with high specificity for diadenosine hexa- and pentaphosphates (Ap6A and Ap5A). Using purified recombinant preparations of these enzymes, we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates. This overlapping specificity of an enzyme for two completely different classes of substrate is not only of enzymological significance, but in addition, this finding provides important new information pertinent to the structure, function, and evolution of the Mutt motif. Moreover, we report that the human protein previously characterized as a diphosphorylated inositol phosphate phosphohydrolase represents the first example, in any animal, of an enzyme that degrades Ap6A and Ap5A, in preference to other diadenosine polyphosphates. The emergence of Ap6A and Ap5A as extracellular effectors and intracellular ion-channel ligands points not only to diphosphorylated inositol phosphate phosphohydrolase as a candidate for regulating signaling by diadenosine polyphosphates, but also suggests that diphosphorylated inositol phosphates may competitively inhibit this process.
AB - Aps1 from Schizosaccharomyces pombe (Ingram, S. W., Stratemann, S. A., and Barnes, L. D. (1999) Biochemistry 38, 3649-3655) and YOR163w from Saccharomyces cerevisiae (Cartwright, J. L., and McLennan, A. G. (1999) J. Biol. Chem. 274, 8604-8610) have both previously been characterized as Mutt family hydrolases with high specificity for diadenosine hexa- and pentaphosphates (Ap6A and Ap5A). Using purified recombinant preparations of these enzymes, we have now discovered that they have an important additional function, namely, the efficient hydrolysis of diphosphorylated inositol polyphosphates. This overlapping specificity of an enzyme for two completely different classes of substrate is not only of enzymological significance, but in addition, this finding provides important new information pertinent to the structure, function, and evolution of the Mutt motif. Moreover, we report that the human protein previously characterized as a diphosphorylated inositol phosphate phosphohydrolase represents the first example, in any animal, of an enzyme that degrades Ap6A and Ap5A, in preference to other diadenosine polyphosphates. The emergence of Ap6A and Ap5A as extracellular effectors and intracellular ion-channel ligands points not only to diphosphorylated inositol phosphate phosphohydrolase as a candidate for regulating signaling by diadenosine polyphosphates, but also suggests that diphosphorylated inositol phosphates may competitively inhibit this process.
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U2 - 10.1074/jbc.274.31.21735
DO - 10.1074/jbc.274.31.21735
M3 - Article
C2 - 10419486
AN - SCOPUS:0033618424
SN - 0021-9258
VL - 274
SP - 21735
EP - 21740
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 31
ER -