diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein

• Published in: The Journal of biological chemistry Vol. 274; no. 31; pp. 21735 - 21740
• Main Authors: Safrany, S.T, Ingram, S.W, Cartwright, J.L, Falck, J.R, McLennan, A.G, Barness, L.D, Shears, S.B
• Format: Journal Article
• Language: English
• Published: United States 30.07.1999
• Subjects: Acid Anhydride Hydrolases - chemistry; Acid Anhydride Hydrolases - metabolism; adenosine phosphates; Amino Acid Sequence; Bacillus - enzymology; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Dinucleoside Phosphates - metabolism; enzyme activity; Escherichia coli Proteins; Humans; hydrolysis; Kinetics; Molecular Sequence Data; phosphoric diester hydrolases; Phosphoric Monoester Hydrolases - chemistry; Phosphoric Monoester Hydrolases - metabolism; Pyrophosphatases - chemistry; Pyrophosphatases - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Schizosaccharomyces - enzymology; Schizosaccharomyces pombe; Schizosaccharomyces pombe Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Substrate Specificity
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.31.21735

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 (Ap(6)A and Ap(5)A). 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 Ap(6)A and Ap(5)A, in preference to other diadenosine polyphosphates. The emergence of Ap(6)A and Ap(5)A 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.