PMID- 10419486
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 31
DP  - 1999 Jul 30
TI  - The 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.
PG  - 21735-40
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 (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.
FAU - Safrany, S T
AU  - Safrany ST
AD  - Inositide Signaling Group, NIEHS, National Institutes of Health, Research
      Triangle Park, North Carolina 27709, USA.
FAU - Ingram, S W
AU  - Ingram SW
FAU - Cartwright, J L
AU  - Cartwright JL
FAU - Falck, J R
AU  - Falck JR
FAU - McLennan, A G
AU  - McLennan AG
FAU - Barnes, L D
AU  - Barnes LD
FAU - Shears, S B
AU  - Shears SB
LA  - eng
GR  - GM31278/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bacterial Proteins)
RN  - 0 (Dinucleoside Phosphates)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Schizosaccharomyces pombe Proteins)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
RN  - EC 3.6.1.- (Pyrophosphatases)
RN  - EC 3.6.1.- (aps1 protein, S pombe)
RN  - EC 3.6.1.- (diphosphoinositol polyphosphate phosphohydrolase)
RN  - EC 3.6.1.- (mutT protein, E coli)
SB  - IM
MH  - Acid Anhydride Hydrolases/chemistry/*metabolism
MH  - Amino Acid Sequence
MH  - Bacillus/enzymology
MH  - Bacterial Proteins/chemistry/*metabolism
MH  - Dinucleoside Phosphates/metabolism
MH  - *Escherichia coli Proteins
MH  - Humans
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Phosphoric Monoester Hydrolases/chemistry/*metabolism
MH  - Pyrophosphatases/chemistry/*metabolism
MH  - Saccharomyces cerevisiae/*enzymology
MH  - Schizosaccharomyces/*enzymology
MH  - Schizosaccharomyces pombe Proteins
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Substrate Specificity
EDAT- 1999/07/27 00:00
MHDA- 1999/07/27 00:01
CRDT- 1999/07/27 00:00
PHST- 1999/07/27 00:00 [pubmed]
PHST- 1999/07/27 00:01 [medline]
PHST- 1999/07/27 00:00 [entrez]
AID - 10.1074/jbc.274.31.21735 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 30;274(31):21735-40. doi: 10.1074/jbc.274.31.21735.