title: The dUTPases from herpes simplex virus type 1 and mouse mammary tumour virus are less specific than the Escherichia coli enzyme.
abstract: The enzyme dUTPase catalyses the hydrolysis of dUTP to dUMP and pyrophosphate, thereby suppressing incorporation of uracil into DNA and providing a pool of dUMP, the precursor of dTTP. Hydrolysis of other nucleotides similar in structure to dUTP would conceivably be physiologically detrimental and high specificity of the reaction seems to be necessary. In this work, we characterize the substrate specificity of the dUTPases from herpes simplex virus type 1 (HSV-1) and mouse mammary tumour virus (MMTV) in comparison to the Escherichia coli enzyme. We tested dCTP, dTTP, UTP and dUDP as substrates. Significantly higher reactivity was observed for the HSV-1 enzyme with dCTP and dTTP and for the MMTV enzyme with dTTP and UTP. The lower substrate specificity of the two virus enzymes compared with the bacterial enzyme is discussed in relation to the DNA precursor metabolism during virus replication.
authors.affiliation: Department of Biochemistry, Center for Chemistry and Chemical Engineering, Lund University, Sweden. olofb@mermaid.molbio.ku.dk
authors.forename: O
authors.initials: O
authors.lastname: Björnberg
authors.forename: P O
authors.initials: PO
authors.lastname: Nyman
mesh_terms: D000818:Animals; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D006868:Hydrolysis; D008324:Mammary Tumor Virus, Mouse / Q000201:enzymology*; D051379:Mice; D011755:Pyrophosphatases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013942:Thymine Nucleotides / Q000378:metabolism
chemical_list: D003845:Deoxycytosine Nucleotides; D003856:Deoxyuracil Nucleotides; D013942:Thymine Nucleotides; C024107:2'-deoxycytidine 5'-triphosphate; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase; C024157:thymidine 5'-triphosphate