Human diadenosine 5′,5′′′-<i>P</i>1,<i>P</i>4-tetraphosphate pyrophosphohydrolase is a member of the MutT family of nucleotide pyrophosphatases

Thorne, Natasha; Hankin, Steven; Wilkinson, Mark C.; Núñez, Cinthia; Barraclough, Roger; McLennan, Alexander G.

doi:10.1042/bj3110717

Cited by 56 publications

(51 citation statements)

References 45 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It therefore seems that recombinant YSA1H migrates anomalously on SDS\PAGE. This phenomenon of slower migration has been observed with other MutT motif proteins, including human Ap % A hydrolase [6] and S. cere isiae Ap ' A hydrolase [18] and might result from incomplete denaturation and SDS binding during sample preparation owing to the stability imparted by the mixed β-sheet core structure that might be a feature of this enzyme family [23]. (Figure 6b, lane 3).…”

Section: Size and Presence Of Ysa1h Protein In Human Cell Extractssupporting

confidence: 58%

“…N-terminal sequencing and electrospray mass spectrometric analysis were performed as described previously [6,18].…”

Section: Other Methodsmentioning

confidence: 99%

“…drolase) [6] and diphosphoinositol polyphosphate phosphohydrolase (DIPP) [7]. DIPP is homologous with the recently described Ap ' A hydrolases from budding and fission yeasts and, like them, is remarkable in its ability to hydrolyse the nonnucleotide diphosphoinositol polyphosphates in addition to the structurally unrelated diadenosine polyphosphates [8].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cloning, expression and characterization of YSA1H, a human adenosine 5′-diphosphosugar pyrophosphatase possessing a MutT motif

Gasmi

Cartwright

McLennan

1999

Biochemical Journal

View full text Add to dashboard Cite

The human homologue of the Saccharomyces cere isiae YSA1 protein, YSA1H, has been expressed as a thioredoxin fusion protein in Escherichia coli. It is an ADP-sugar pyrophosphatase with similar activities towards ADP-ribose and ADP-mannose. Its activities with ADP-glucose and diadenosine diphosphate were 56 % and 20 % of that with ADP-ribose respectively, whereas its activity towards other nucleoside 5h-diphosphosugars was typically 2-10 %. cADP-ribose was not a substrate. The products of ADP-ribose hydrolysis were AMP and ribose 5-phosphate. K m and k cat values with ADP-ribose were 60 µM and 5.5 s −" respectively. The optimal activity was at alkaline pH (7.4-9.0) with 2.5-5 mM Mg# + or 100-250 µM Mn# + ions ; fluoride was inhibitory, with an IC

show abstract

Section: Size and Presence Of Ysa1h Protein In Human Cell Extractssupporting

confidence: 58%

“…N-terminal sequencing and electrospray mass spectrometric analysis were performed as described previously [6,18].…”

Section: Other Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cloning, expression and characterization of YSA1H, a human adenosine 5′-diphosphosugar pyrophosphatase possessing a MutT motif

Gasmi

Cartwright

McLennan

1999

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Other Methods-Protein concentrations were estimated by the Coomassie Blue binding method (29) and protein molecular masses were determined by electrospray mass spectrometry as previously described (30).…”

Section: Cloning Of C Elegans Ap 4 a Hydrolase As A Glutathione S-trmentioning

confidence: 99%

Analysis of the Catalytic and Binding Residues of the Diadenosine Tetraphosphate Pyrophosphohydrolase from Caenorhabditis elegans by Site-directed Mutagenesis

Abdelghany¹,

Bailey²,

Blackburn³

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Homogeneous recombinant (asymmetrical) Ap 4 A hydrolases (EC 3.6.1.17) from human [24], narrow-leafed lupin (Lupinus angustifolius) [25] and Caenorhabditis elegans [26] were obtained as described. The lupin enzyme was kindly donated by Dr D. Maksel and Dr K. Gayler (University of Melbourne, Melbourne, Australia).…”

Section: Experimental Enzymesmentioning

confidence: 99%

Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases

Guranowski¹,

Starzyńska²,

McLennan

et al. 2003

Biochemical Journal

View full text Add to dashboard Cite

Dinucleoside 5 ,5 -P 1 ,P n -polyphosphates, and particularly the diadenosine compounds, have been implicated in extracellular purinergic signalling and in various intracellular processes, including DNA metabolism, tumour suppression and stress responses. If permitted to accumulate, they may also be toxic. One approach to understanding their function is through the various specific degradative enzymes that regulate their levels. Eight adenosine-5 -O-phosphorylated polyols (derivatives of glycerol, erythritol and pentaerythritol) and 11 adenosine-5 -O-phosphorothioylated polyols (derivatives of glycerol, erythritol, pentaerythritol, butanediol and pentanediol) have been tested as inhibitors of specific diadenosine tetraphosphate (Ap 4 A) hydrolases. Of these two groups of novel nucleotides, the adenosine-5 -O-phosphorothioylated polyols were generally stronger inhibitors than their adenosine-5 -O-phosphorylated counterparts. 1,4-Di(adenosine-5 -O-phosphorothio) erythritol appeared to be the strongest inhibitor of (asymmetrical) Ap 4 A hydrolases (EC 3.6.1.17) from both lupin and human, with K i values of 0.15 µM and 1.5 µM respectively. Of eight adenosine-5 -Ophosphorylated polyols, 1,4-di(adenosine-5 -O-phospho) erythritol was the only compound that inhibited the lupin enzyme. Two derivatives of pentaerythritol, di(adenosine-5 -O-phosphorothio)-di(phosphorothio) pentaerythritol and tri(adenosine-5 -Ophosphorothio)-phosphorothio-pentaerythritol, proved to be the strongest inhibitors of the prokaryotic (symmetrical) Ap 4 A hydrolase (EC 3.6.1.41) so far reported. The estimated K i values were 0.04 µM and 0.08 µM respectively. All of these inhibitors were competitive with respect to Ap 4 A. These new selectively acting Ap 4 A analogues should prove to be valuable tools for further studies of Ap 4 A function and of the enzymes involved in its metabolism.

show abstract

Human diadenosine 5′,5′′′-P1,P4-tetraphosphate pyrophosphohydrolase is a member of the MutT family of nucleotide pyrophosphatases

Cited by 56 publications

References 45 publications

Cloning, expression and characterization of YSA1H, a human adenosine 5′-diphosphosugar pyrophosphatase possessing a MutT motif

Cloning, expression and characterization of YSA1H, a human adenosine 5′-diphosphosugar pyrophosphatase possessing a MutT motif

Analysis of the Catalytic and Binding Residues of the Diadenosine Tetraphosphate Pyrophosphohydrolase from Caenorhabditis elegans by Site-directed Mutagenesis

Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases

Contact Info

Product

Resources

About