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

Stephen T. Safrany, Stephen W. Ingram, Jared L. Cartwright, J. R. Falck, Alexander G. McLennan, Larry D. Barnes, Stephen B. Shears

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)21735-21740
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number31
DOIs
StatePublished - Jul 30 1999

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Polyphosphates
Schizosaccharomyces
Hydrolases
Substrate Specificity
Phosphoric Monoester Hydrolases
Yeast
Inositol Phosphates
Saccharomyces cerevisiae
Substrates
Proteins
Enzymes
Biochemistry
Inositol
Ion Channels
Hydrolysis
Animals
Ligands
diadenosine 5',5''''-P1,P6-hexaphosphate
P(1),P(5)-di(adenosine-5'-)pentaphosphate

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Safrany, Stephen T.; Ingram, Stephen W.; Cartwright, Jared L.; Falck, J. R.; McLennan, Alexander G.; Barnes, Larry D.; Shears, Stephen B.

In: Journal of Biological Chemistry, Vol. 274, No. 31, 30.07.1999, p. 21735-21740.

Research output: Contribution to journalArticle

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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.

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