Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical] is an enzyme that in humans is encoded by the NUDT2gene.[1][2][3]
This gene encodes a member of the MutT family of nucleotide pyrophosphatases, a subset of the larger NUDIX hydrolase family. The gene product possesses a modification of the MutT sequence motif found in certain nucleotide pyrophosphatases. The enzyme asymmetrically hydrolyzes Ap4A to yield AMP and ATP and is responsible for maintaining the intracellular level of the dinucleotide Ap4A, the function of which has yet to be established. This gene may be a candidate tumor suppressor gene. Alternative splicing has been observed at this locus and three transcript variants, all encoding the same protein, have been identified.[3]
↑McLennan AG, Flannery AV, Morten JE, Ridanpaa M (Apr 1998). "Chromosomal localization of the human diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase (Ap4A hydrolase) gene (APAH1) to 9p13". Genomics. 47 (2): 307–9. doi:10.1006/geno.1997.5092. PMID9479504.
Bessman MJ, Frick DN, O'Handley SF (1996). "The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes". J. Biol. Chem. 271 (41): 25059–62. doi:10.1074/jbc.271.41.25059. PMID8810257.
Pinto RM, Costas MJ, Fernández A, et al. (1991). "Dinucleoside tetraphosphatase from human blood cells. Purification and characterization as a high specific activity enzyme recognized by an anti-rat tetraphosphatase antibody". FEBS Lett. 287 (1–2): 85–8. doi:10.1016/0014-5793(91)80021-T. PMID1652465.
Hankin S, Matthew N, Thorne H, McLennan AG (1995). "Diadenosine 5',5"'-P1,P4-tetraphosphate hydrolase is present in human erythrocytes, leukocytes and platelets". Int. J. Biochem. Cell Biol. 27 (2): 201–6. doi:10.1016/1357-2725(94)00076-N. PMID7767787.
Lazewska D, Starzyńska E, Guranowski A (1993). "Human placental (Asymmetrical) diadenosine 5',5-P1,P4-tetraphosphate hydrolase: purification to homogeneity and some properties". Protein Expr. Purif. 4 (1): 45–51. doi:10.1006/prep.1993.1007. PMID8381042.
Rotllán P, Rodríguez-Ferrer CR, Asensio AC, Oaknin S (1998). "Potent inhibition of specific diadenosine polyphosphate hydrolases by suramin". FEBS Lett. 429 (2): 143–6. doi:10.1016/S0014-5793(98)00579-1. PMID9650578.
Vartanian A, Alexandrov I, Prudowski I, et al. (1999). "Ap4A induces apoptosis in human cultured cells". FEBS Lett. 456 (1): 175–80. doi:10.1016/S0014-5793(99)00956-4. PMID10452553.
Guranowski A, Galbas M, Hartmann R, Justesen J (2000). "Selective degradation of 2'-adenylated diadenosine tri- and tetraphosphates, Ap(3)A and Ap(4)A, by two specific human dinucleoside polyphosphate hydrolases". Arch. Biochem. Biophys. 373 (1): 218–24. doi:10.1006/abbi.1999.1556. PMID10620341.
Abdelghany HM, Gasmi L, Cartwright JL, et al. (2002). "Cloning, characterisation and crystallisation of a diadenosine 5',5"'-P(1),P(4)-tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans". Biochim. Biophys. Acta. 1550 (1): 27–36. doi:10.1016/S0167-4838(01)00263-1. PMID11738085.
Guranowski A, Sillero A, Günther Sillero MA (2003). "Selective splitting of 3'-adenylated dinucleoside polyphosphates by specific enzymes degrading dinucleoside polyphosphates". Acta Biochim. Pol. 50 (1): 123–30. PMID12673352.
Pitcher WH, Kirby TW, DeRose EF, London RE (2003). "Metabolic transformation of AZTp4A by Ap4A hydrolase regenerates AZT triphosphate". Antiviral Res. 58 (3): 227–33. doi:10.1016/S0166-3542(03)00003-2. PMID12767470.
Swarbrick JD, Buyya S, Gunawardana D, et al. (2005). "Structure and substrate-binding mechanism of human Ap4A hydrolase". J. Biol. Chem. 280 (9): 8471–81. doi:10.1074/jbc.M412318200. PMID15596429.
Swarbrick JD, Buyya S, Gunawardana D, et al. (2005). "1H, 13C, and 15N resonance assignments of the 17 kDa Ap4A hydrolase from Homo sapiens in the presence and absence of ATP". J. Biomol. NMR. 31 (2): 181–2. doi:10.1007/s10858-004-7440-4. PMID15772762.
