Alexander G McLennan

Summary

Affiliation: University of Liverpool
Country: UK

Publications

  1. ncbi request reprint Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate
    David I Fisher
    Cell Regulation and Signalling Group, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom
    J Biol Chem 277:47313-7. 2002
  2. pmc Characterization of a nudix hydrolase from Deinococcus radiodurans with a marked specificity for (deoxy)ribonucleoside 5'-diphosphates
    David I Fisher
    School of Biological Sciences, Biosciences Building, University of Liverpool, P, O, Box 147, Liverpool L69 7ZB, UK
    BMC Biochem 5:7. 2004
  3. ncbi request reprint Characterization of the Mn2+-stimulated (di)adenosine polyphosphate hydrolase encoded by the Deinococcus radiodurans DR2356 nudix gene
    David I Fisher
    School of Biological Sciences, Biosciences Building, University of Liverpool, P O Box 147, Liverpool, UK
    Arch Microbiol 186:415-24. 2006
  4. doi request reprint Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?
    Alexander G McLennan
    Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown St, Liverpool, L69 7ZB, UK
    Cell Mol Life Sci 70:373-85. 2013
  5. pmc Cloning and characterisation of hAps1 and hAps2, human diadenosine polyphosphate-metabolising Nudix hydrolases
    Nick R Leslie
    Division of Cell Signalling, School of Life Sciences, The University of Dundee, Dundee, DD1 5EH, UK
    BMC Biochem 3:20. 2002
  6. ncbi request reprint Chromosomal localization of the human diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase (Ap4A hydrolase) gene (APAH1) to 9p13
    A G McLennan
    School of Biological Sciences, University of Liverpool, United Kingdom
    Genomics 47:307-9. 1998
  7. ncbi request reprint Dinucleoside polyphosphates-friend or foe?
    A G McLennan
    School of Biological Sciences, Life Sciences Building, University of Liverpool, Crown Street, L69 7ZB, Liverpool, UK
    Pharmacol Ther 87:73-89. 2000
  8. doi request reprint Ametabolic embryos of Artemia franciscana accumulate DNA damage during prolonged anoxia
    Alexander G McLennan
    Cell Regulation and Signalling Division, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
    J Exp Biol 212:785-9. 2009
  9. ncbi request reprint The Nudix hydrolase superfamily
    A G McLennan
    School of Biological Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, United Kingdom
    Cell Mol Life Sci 63:123-43. 2006
  10. ncbi request reprint Decapitation: poxvirus makes RNA lose its head
    Alexander G McLennan
    School of Biological Sciences, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK
    Trends Biochem Sci 32:297-9. 2007

Collaborators

Detail Information

Publications37

  1. ncbi request reprint Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate
    David I Fisher
    Cell Regulation and Signalling Group, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom
    J Biol Chem 277:47313-7. 2002
    ..radiodurans DR2356 enzyme and for the DIPP subfamily. In the latter case, generation of the glycolytic activator ribose 1,5-bisphosphate may be a new function for these enzymes...
  2. pmc Characterization of a nudix hydrolase from Deinococcus radiodurans with a marked specificity for (deoxy)ribonucleoside 5'-diphosphates
    David I Fisher
    School of Biological Sciences, Biosciences Building, University of Liverpool, P, O, Box 147, Liverpool L69 7ZB, UK
    BMC Biochem 5:7. 2004
    ..Characterisation of these hydrolases is necessary to understand the reason for their presence. Here, we report the cloning and characterisation of the DR0975 gene product, a nudix hydrolase that appears to be unique to this organism...
  3. ncbi request reprint Characterization of the Mn2+-stimulated (di)adenosine polyphosphate hydrolase encoded by the Deinococcus radiodurans DR2356 nudix gene
    David I Fisher
    School of Biological Sciences, Biosciences Building, University of Liverpool, P O Box 147, Liverpool, UK
    Arch Microbiol 186:415-24. 2006
    ..The Mn-requirement and induction in stationary phase suggest that DR2356 may have a specific role in maintenance mode metabolism in stationary phase as Mn(2+) accumulates...
  4. doi request reprint Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?
    Alexander G McLennan
    Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown St, Liverpool, L69 7ZB, UK
    Cell Mol Life Sci 70:373-85. 2013
    ....
  5. pmc Cloning and characterisation of hAps1 and hAps2, human diadenosine polyphosphate-metabolising Nudix hydrolases
    Nick R Leslie
    Division of Cell Signalling, School of Life Sciences, The University of Dundee, Dundee, DD1 5EH, UK
    BMC Biochem 3:20. 2002
    ..The human genome contains at least 18 genes for Nudix hydrolase enzymes. Many have similar functions to one another. In order to understand their roles in cell physiology, these proteins must be characterised...
  6. ncbi request reprint Chromosomal localization of the human diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase (Ap4A hydrolase) gene (APAH1) to 9p13
    A G McLennan
    School of Biological Sciences, University of Liverpool, United Kingdom
    Genomics 47:307-9. 1998
    ..Given that the FHIT gene at 3p14.2, which encodes a diadenosine 5',5"'-P1,P3-triphosphate (AP3A) hydrolase, is a candidate tumor suppressor, APAH1 should also be considered a potential tumor suppressor...
  7. ncbi request reprint Dinucleoside polyphosphates-friend or foe?
    A G McLennan
    School of Biological Sciences, Life Sciences Building, University of Liverpool, Crown Street, L69 7ZB, Liverpool, UK
    Pharmacol Ther 87:73-89. 2000
    ..It is concluded that the roles of friend and foe are not incompatible, but are distinguished by the concentration range of nucleotide achieved under different circumstances...
  8. doi request reprint Ametabolic embryos of Artemia franciscana accumulate DNA damage during prolonged anoxia
    Alexander G McLennan
    Cell Regulation and Signalling Division, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
    J Exp Biol 212:785-9. 2009
    ....
  9. ncbi request reprint The Nudix hydrolase superfamily
    A G McLennan
    School of Biological Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, United Kingdom
    Cell Mol Life Sci 63:123-43. 2006
    ....
  10. ncbi request reprint Decapitation: poxvirus makes RNA lose its head
    Alexander G McLennan
    School of Biological Sciences, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK
    Trends Biochem Sci 32:297-9. 2007
    ..A Nudix hydrolase encoded by the viral D10 gene decaps these mRNAs, thus targeting them for destruction independently of cellular systems. This finding has several implications for virus evolution and the regulation of RNA decapping...
  11. ncbi request reprint Regulation of dinucleoside polyphosphate pools by the YgdP and ApaH hydrolases is essential for the ability of Salmonella enterica serovar typhimurium to invade cultured mammalian cells
    Thamir M Ismail
    School of Biological Sciences and Department of Medical Microbiology and Genito urinary Medicine, University of Liverpool, Liverpool L69 7ZB, United Kingdom
    J Biol Chem 278:32602-7. 2003
    ..The increase in intracellular NpnN in the mutants appears to cause changes in gene expression that limit the ability of S. Typhimurium to adhere to and invade mammalian cells...
  12. pmc Mammalian NADH diphosphatases of the Nudix family: cloning and characterization of the human peroxisomal NUDT12 protein
    Salama R Abdelraheim
    Cell Regulation and Signalling Group, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
    Biochem J 374:329-35. 2003
    ..NUDT12 may act to regulate the concentration of peroxisomal nicotinamide nucleotide cofactors required for oxidative metabolism in this organelle...
  13. ncbi request reprint Analysis of the catalytic and binding residues of the diadenosine tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans by site-directed mutagenesis
    Hend M Abdelghany
    School of Biological Sciences, Biosciences Building, University of Liverpool, P O Box 147, Liverpool L69 7ZB, United Kingdom
    J Biol Chem 278:4435-9. 2003
    ....
  14. pmc The Caenorhabditis elegans Y87G2A.14 Nudix hydrolase is a peroxisomal coenzyme A diphosphatase
    Salama R Abdelraheim
    School of Biological Sciences, Life Sciences Building, University of Liverpool, P, O, Box 147, Liverpool L69 7ZB, UK
    BMC Biochem 3:5. 2002
    ..In order to understand the reasons for the particular spectrum possessed by a given organism, the substrate specificity and function of different family members must be established...
  15. ncbi request reprint GTP:GTP guanylyltransferase: trapping procedures for detecting and characterizing chemical nature of enzyme-nucleotide phosphoramidate reaction intermediate
    Jared L Cartwright
    School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom
    Methods Enzymol 354:251-60. 2002
  16. ncbi request reprint Correlation of intracellular diadenosine triphosphate (Ap3A) with apoptosis in Fhit-positive HEK293 cells
    David I Fisher
    Cell Regulation and Signalling Group, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
    Cancer Lett 259:186-91. 2008
    ..510pmol/10(6)cells with etoposide. These results support the view that Ap3A is the in vivo Fhit ligand and that an inhibition of Fhit activity is a key element in Fhit-mediated apoptosis...
  17. ncbi request reprint The MutT motif-containing ORF163w protein from the yeast Saccharomyces cerevisiae encodes a (di)nucleoside polyphosphate hydrolase
    J L Cartwright
    School of Biological Sciences, University of Liverpool, U K
    Biochem Soc Trans 25:S580. 1997
  18. ncbi request reprint Diadenosine polyphosphates are largely ineffective as agonists at natively expressed P2Y(1) and P2Y(2) receptors on cultured human saphenous vein endothelial cells
    A R Conant
    Cardiothoracic Centre, Liverpool NHS Trust, UK
    J Vasc Res 37:548-55. 2000
    ..We would therefore predict that the diadenosine polyphosphates have only a limited vasodilatory role in human saphenous veins...
  19. ncbi request reprint The Saccharomyces cerevisiae YOR163w gene encodes a diadenosine 5', 5"'-P1,P6-hexaphosphate (Ap6A) hydrolase member of the MutT motif (Nudix hydrolase) family
    J L Cartwright
    School of Biological Sciences, Life Sciences Building, University of Liverpool, P O Box 147, Liverpool L69 7ZB, United Kingdom
    J Biol Chem 274:8604-10. 1999
    ..3 mM and F- (noncompetitively) with a Ki of 80 microM. Its function may be to eliminate potentially toxic dinucleoside polyphosphates during sporulation...
  20. pmc The g5R (D250) gene of African swine fever virus encodes a Nudix hydrolase that preferentially degrades diphosphoinositol polyphosphates
    Jared L Cartwright
    School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
    J Virol 76:1415-21. 2002
    ..These results suggest a possible role for g5Rp in regulating a stage of viral morphogenesis involving diphosphoinositol polyphosphate-mediated membrane trafficking...
  21. pmc The mouse Nudt7 gene encodes a peroxisomal nudix hydrolase specific for coenzyme A and its derivatives
    L Gasmi
    School of Biological Sciences, Life Sciences Building, University of Liverpool, P O Box 147, Liverpool L69 7ZB, UK
    Biochem J 357:33-8. 2001
    ..The function of the NUDT7 enzyme may be the elimination of oxidized CoA from peroxisomes, or the regulation of CoA and acyl-CoA levels in this organelle in response to metabolic demand...
  22. ncbi request reprint The Saccharomyces cerevisiae PCD1 gene encodes a peroxisomal nudix hydrolase active toward coenzyme A and its derivatives
    J L Cartwright
    Cell Regulation and Signalling Group and Centre for Cell Imaging, School of Biological Sciences, University of Liverpool, Life Sciences Building, Liverpool L69 7ZB, United Kingdom
    J Biol Chem 275:32925-30. 2000
    ..The function of Pcd1p may be to remove potentially toxic oxidized CoA disulfide from peroxisomes in order to maintain the capacity for beta-oxidation of fatty acids...
  23. ncbi request reprint The NADH diphosphatase encoded by the Saccharomyces cerevisiae NPY1 nudix hydrolase gene is located in peroxisomes
    S R AbdelRaheim
    School of Biological Sciences, University of Liverpool, United Kingdom
    Arch Biochem Biophys 388:18-24. 2001
    ..This function may be the regulation of nicotinamide coenzyme concentrations independently of those in other compartments or the elimination of oxidized nucleotide derivatives from the peroxisomal environment...
  24. ncbi request reprint Cloning, characterisation and crystallisation of a diadenosine 5',5"'-P(1),P(4)-tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans
    H M Abdelghany
    School of Biological Sciences, University of Liverpool, UK
    Biochim Biophys Acta 1550:27-36. 2001
    ..Complete structural determination of the C. elegans Ap4A hydrolase will help determine the basis of this grouping...
  25. ncbi request reprint The MutT motif family of nucleotide phosphohydrolases in man and human pathogens (review)
    A G McLennan
    School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK
    Int J Mol Med 4:79-89. 1999
    ..This protein family, therefore, occupies a position of some importance in controlling human health and disease...
  26. pmc Cloning, expression and characterization of YSA1H, a human adenosine 5'-diphosphosugar pyrophosphatase possessing a MutT motif
    L Gasmi
    School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB, U K
    Biochem J 344:331-7. 1999
    ..Hence the function of YSA1H might be to remove free ADP-ribose arising from NAD(+) and protein-bound poly- and mono-(ADP-ribose) turnover to prevent the occurrence of non-enzymic protein glycation...
  27. ncbi request reprint Molecular cloning of diadenosine tetraphosphatase from pig small intestinal mucosa and identification of sequence blocks common to diadenosine polyphosphate hydrolases and phosphorylases
    S Hankin
    School of Biological Sciences, University of Liverpool, U K
    Int J Biochem Cell Biol 29:317-23. 1997
    ..These sequence similarities may have arisen by convergent evolution...
  28. ncbi request reprint Synthesis of dinucleoside tetraphosphates in transfected cells by a firefly luciferase reporter gene
    G A Murphy
    School of Biological Sciences, University of Liverpool, Biosciences Building, Liverpool L69 7ZB, UK
    Cell Mol Life Sci 61:497-501. 2004
    ..This observation also points to a useful non-invasive procedure for the specific enhancement of intracellular Ap4N for studies directed at understanding the functions of these compounds...
  29. ncbi request reprint Structure and substrate-binding mechanism of human Ap4A hydrolase
    James D Swarbrick
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Biol Chem 280:8471-81. 2005
    ..This may have important implications in the mechanism of substrate recognition in this class of enzymes...
  30. ncbi request reprint Crystallization of a complex of Caenorhabditis elegans diadenosine tetraphosphate hydrolase and a non-hydrolysable substrate analogue, AppCH2ppA
    Scott Bailey
    Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, England
    Acta Crystallogr D Biol Crystallogr 58:526-8. 2002
    ..6, b = 36.8, c = 68.9 A, beta = 114.2 degrees, and diffract to approximately 2.0 A. Determination of the structure of this complex will provide insights into the substrate specificity and catalytic activity of this class of enzymes...
  31. ncbi request reprint Folate synthesis: an old enzyme identified
    Alexander G McLennan
    Structure 15:891-2. 2007
    ....
  32. pmc Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases
    Andrzej Guranowski
    Department of Biochemistry and Biotechnology, University of Agriculture, 60 637 Poznan, Poland
    Biochem J 373:635-40. 2003
    ..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...
  33. ncbi request reprint Cloning, expression and characterisation of a human Nudix hydrolase specific for adenosine 5'-diphosphoribose (ADP-ribose)
    Shengrong Lin
    State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, PR China
    Biochim Biophys Acta 1594:127-35. 2002
    ..However, any relationship between the NUDT9 species and the previously reported ADPRibases remains to be established...
  34. ncbi request reprint The specific, submicromolar-Km ADP-ribose pyrophosphatase purified from human placenta is enzymically indistinguishable from recombinant NUDT9 protein, including a selectivity for Mn2+ as activating cation and increase in Km for ADP-ribose, both elicited
    António Carloto
    Unidad de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Extremadura, 06080 Badajoz, Spain
    Biochim Biophys Acta 1760:1545-51. 2006
    ..The results are discussed in relation to the proposed roles for ADP-ribose in oxidative/nitrosative stress and for ADP-ribose pyrophosphatase as a protective enzyme whose function is to limit the intracellular accumulation of ADP-ribose...
  35. ncbi request reprint The crystal structure of diadenosine tetraphosphate hydrolase from Caenorhabditis elegans in free and binary complex forms
    Scott Bailey
    Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, United Kingdom
    Structure 10:589-600. 2002
    ..These results suggest how the enzyme can catalyze the hydrolysis of a range of related dinucleoside tetraphosphate, but not triphosphate, compounds through precise orientation of key elements of the substrate...
  36. ncbi request reprint 1H, 13C, and 15N resonance assignments of the 17 kDa Ap4A hydrolase from Homo sapiens in the presence and absence of ATP
    James D Swarbrick
    J Biomol NMR 31:181-2. 2005
  37. ncbi request reprint Characterisation of a bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) from Drosophila melanogaster
    Lucinda Winward
    Division of Cell Signalling, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Int J Biochem Cell Biol 39:943-54. 2007
    ....