The mouse guanylate kinase double mutant E72Q/D103N is a functional adenylate kinase.
Guanylate kinase catalyzes the phosphorylation of either GMP to GDP or dGMP to dGDP and is an important enzyme in nucleotide metabolic pathways. Because of its essential intracellular role, guanylate kinase is a target for a number of cancer chemotherapeutic agents such as 6-thioguanine and 8-azaguanine and is involved in antiviral drug activation. Guanylate kinase shares a similarity in function and structure to other nucleoside monophosphate kinases especially with that of the well-studied adenylate kinase. Amino acid substitutions were made within the GMP binding site of mouse guanylate kinase to alter the polarity of the side chains that interact with GMP as a means of evaluating the role that these residues play on substrate interaction. One of these mutants, E72Q/D103N, was shown by functional complementation and enzyme assays to embody both guanylate kinase activity and a novel adenylate kinase activity.
Stolworthy
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Department of Pharmaceutical Sciences, P.O. Box 646534, Washington State University, Pullman, WA 99164-6534, USA.
Black
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D000249:Adenosine Monophosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001216:Asparagine / Q000737:chemistry; D001665:Binding Sites; D018076:DNA, Complementary / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D005973:Glutamine / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000378:metabolism; D051528:Guanylate Kinases; D051379:Mice; D008956:Models, Chemical; D016296:Mutagenesis; D009154:Mutation; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics* / Q000378:metabolism; D013053:Spectrophotometry; D013379:Substrate Specificity; D013997:Time Factors
D018076:DNA, Complementary; D005973:Glutamine; D000249:Adenosine Monophosphate; D001216:Asparagine; D006157:Guanosine Monophosphate; D000263:Adenylate Kinase; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases