Crystal structures of equine herpesvirus type-4 thymidine kinase (EHV4-TK) in complex with (i). thymidine and ADP, (ii). thymidine and SO(4) and the bisubstrate analogs, (iii). TP(4)A, and (iv). TP(5)A have been solved. Additionally, the structure of herpes simplex virus type-1 thymidine kinase (HSV1-TK) in complex with TP(5)A has been determined. These are the first structures of nucleoside ki...

The thymidine kinases (TK) of alphaherpesviruses phosphorylate nucleosides, allowing viral replication in non-dividing cells. They also phosphorylate acyclovir (ACV), a specific antiviral when modified. Despite encoding a TK homolog, Kaposi’s sarcoma-associated herpesvirus (KSHV), a gammaherpesvirus, is relatively immune to the effects of ACV. In this issue, Gill et al (2015) show that rather t...

We have studied the effect of pH on the interactions between thymidine kinase, thymidine triphosphate, and 5'-amino-2',5'-dideoxythymidine (S'-Ad'l'hd) in purified preparations of the enzyme and in intact 647V cells, a human bladder cancer cell line. Thymidine kinase is competitively inhibited by S'-AdThd. dI'll' feedback inhibits in a noncompetitive fashion. However, S'-AdThd partially reverse...

We have studied the effect of pH on the interactions between thymidine kinase, thymidine triphosphate, and 5'-amino-2',5'-dideoxythymidine (S'-Ad'l'hd) in purified preparations of the enzyme and in intact 647V cells, a human bladder cancer cell line. Thymidine kinase is competitively inhibited by S'-AdThd. dI'll' feedback inhibits in a noncompetitive fashion. However, S'-AdThd partially reverse...

We have studied the effect of pH on the interactions between thymidine kinase, thymidine triphosphate, and 5'-amino-2',5'-dideoxythymidine (5'-AdThd) in purified preparations of the enzyme and in intact 647V cells, a human bladder cancer cell line. Thymidine kinase is competitively inhibited by 5'-AdThd. dTTP feedback inhibits in a noncompetitive fashion. However, 5'-AdThd partially reverses th...

Thymidine kinase activity in rat C6 glioma cells is inhibited by 50 to 70% after 4 hr incubation with 20 mM D-glucosamine. The inhibition is uncompetitive with respect to thymidine, reducing both the apparent Km and Vmax of the enzyme. The inhibition does not appear to be caused by the reversible combination of the enzyme with a cytoplasmic inhibitor, including D-glucosamine and its metabolites...

Accumulating evidence indicates that the initiation of deoxyribonucleic acid synthesis is intimately associated with the appearance of elevated levels of enzymes involved in the synthesis of thymidine triphosphate. Thus, enhanced levels of such enzymes as thymidine kinase (l-11), thymidylate kinase (5-7, 12I4), thymidine diphosphate kinase (6,7), thymidylate synthetase (10, 15, 16), and deoxycy...

The behavior of the activities of thymidine metabolizing enzymes, dihydrothymine dehydrogenase (EC 1.3.1.2) and thymidine phosphorylase (EC 2.4.2.4) for thymidine degradation, thymidine kinase (EC 2.7.1.75) and thymidylate synthase (EC 2.1.1.45) for DNA synthesis, was elucidated in cytosolic extracts from normal human lymphocytes and 13 human leukemia-lymphoma cell lines. In the normal human ly...