Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.21 (thymidine kinase)
7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Replication of equine herpesvirus type 1 (EHV-1) was sensitive to 9-(1,3-dihydroxy-2-propoxymethyl)guanine(DHPG) but relatively resistant to E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU). Likewise, plaque formation by EHV-1 was inhibited by DHPG, but not by BVDU. Plaque formation by a thymidine kinase-negative (tk-) mutant of EHV-1 was not inhibited by DHPG. In order to investigate biochemical mechanisms determining the differential sensitivity of EHV-1 to these drugs, the EHV-1-encoded thymidine kinase enzyme activity (TK)1 was partially purified from EHV-1-infected cells and analyzed. The EHV-1-induced enzyme utilized both ATP and CTP as phosphate donors and differed in relative electrophoretic mobility from the TKs of mock-infected and HSV-1-infected cells. Phosphorylation of 3H-dThd by the EHV-1 TK was inhibited by AraT, IdUrd, BVDU, and DHPG. The EHV-1 TK phosphorylated 125I-dCyd and 3H-ACV. The results indicate that EHV-1 encodes a pyrimidine deoxyribonucleoside kinase with broad nucleoside substrate specificity. These observations suggest that the failure of BVDU to inhibit EHV-1 replication is not attributable to an inability of the EHV-1 TK to phosphorylate BVDU, but may result from the incapacity of the viral TK to convert BVDU monophosphate to the triphosphate or from lack of inhibitory effect of BVDU triphosphate on viral DNA polymerase reactions.
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PMID:Phosphorylation of nucleoside analogs by equine herpesvirus type 1 pyrimidine deoxyribonucleoside kinase. 302 47

Resistance of human CCRF-CEM leukemic cells in tissue culture to 5-fluoro-2'-deoxyuridine (FdUrd) has been examined following a single drug exposure (FS sublines). In two FS sublines generated by soft agar cloning of FdUrd sensitive cells in the presence of 10 nM FdUrd, the level of drug resistance was maintained at 22- to 30-fold following 1 month growth in the absence of FdUrd. Characteristic of the FS sublines was a decreased accumulation and retention of free intracellular 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) averaging 3% of FdUrd sensitive cells, a more rapid rate of disappearance of free FdUMP and FdUMP-bound thymidylate synthase (EC 2.1.1.45, 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase), and enhanced alkaline and acid phosphatase activities. There was no significant difference in the number of nucleoside transport sites per cell among the FS sublines and FdUrd-sensitive cells, indicating that the decreased accumulation of FdUMP in the resistant sublines was not the result of impaired FdUrd transport across the plasma membrane. The more rapid turnover of FdUMP-bound TMP synthase observed in the FS sublines was neither accompanied by a decreased stability of the TMP synthase-FdUMP-5,10-methylenetetrahydrofolate ternary complex, nor an enhanced rate of degradation of FdUrd to the less potent agent, 5-fluorouracil. In addition, the growth rates of the two FS sublines were similar to that of FdUrd sensitive cells in medium containing hypoxanthine, methotrexate, and thymidine, indicating that there was no depletion of thymidine kinase (EC 2.7.1.21, ATP : thymidine-5'-phosphotransferase) in the FS sublines. Therefore, we propose that enhanced activities of acid and alkaline phosphatases, which influence the intracellular accumulation and retention of FdUMP, are important determinants of stable FdUrd resistance in CCRF-CEM cells.
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PMID:Resistance of CCRF-CEM cloned sublines to 5-fluorodeoxyuridine associated with enhanced phosphatase activities. 315 14

The dominating thymidine kinase activity in mononuclear white blood cells from three patients with untreated acute myelocytic leukemia (AML) was compared with TK 1 from phytohemagglutinin-stimulated and TK 2 from unstimulated, normal lymphocytes. The enzyme activity in the AML cells and the stimulated lymphocytes was found to be in the same range. Regarding the combined thymidine and dTTP kinetics, the enzymes from the three AML patients resembled TK 1, but the ATP kinetics were different and the molecular weights were lower, as previously found for thymidine kinases from other leukemic cells. Therefore, the designation TK-1-onc is suggested for the thymidine kinases from the AML cells.
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PMID:Thymidine kinase in human leukemia. Expression of the lymphoblastic isoenzyme in three patients with acute myelocytic leukemia. 316 55

The dominating thymidine kinase isoenzyme was examined in mononuclear leucocytes from two patients, one with acute and one with chronic lymphatic leukemia. The two isoenzymes exhibited Michaelis-Menten substrate kinetics with ATP and cooperative inhibition kinetics with dTTP. The substrate kinetics with thymidine were different. According to the enzymatic properties the isoenzymes from the acute and chronic lymphatic cells were designated TK 3 and TK 4, respectively. Comparison with the isoenzymes in normal lymphocytes (TK 1, TK 2) and in acute monocytic leukemic cells (TK 3, TK 4) indicated the existence of three thymidine kinase isoenzymes in human leukemic cells which differed from the two isoenzymes in normal human lymphocytes.
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PMID:Thymidine kinase isoenzymes in human acute and chronic lymphatic leukemia. 345 77

Two forms of deoxythymidine kinase were separated from human tonsillar lymphocytes on DEAE-Sephadex column (peak 1 and peak 2 isoenzymes) and identified by gel electrophoresis. Both isoenzymes were found in freshly prepared lymphocytes as well as in lymphocytes cultured in the presence or absence of phytohaemagglutinin, but freshly prepared and phytohaemagglutinin-stimulated cells contained higher activity of peak 1 isoenzyme than the cultured, non-stimulated ones. Kinetic properties and feed-back inhibition of the two separated isoenzymes were compared. The apparent Km values of isoenzyme 1 and 2 were 4 microM and 5 microM for thymidine and were 0.15 mM and 0.12 mM for ATP, respectively. Isoenzyme 1 was found to be more sensitive to heat denaturation at 55 degrees C, and to feedback inhibition by dTTP than isoenzyme 2. On the contrary, isoenzyme 1 was more resistant to dCTP inhibition than the other one. It is concluded that the isoenzyme 1 activity correlates with the synthesis of DNA, while the activity of isoenzyme 2 seems to be constant. The high activity of isoenzyme 1 in freshly isolated tonsil lymphocytes supports their active proliferation in the organ.
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PMID:Pyrimidine salvage enzymes in human tonsil lymphocytes. I. Separation and properties of thymidine kinase isoenzymes. 383 77

Two thymidine kinase isoenzymes, TK 3 and TK 4, from mononuclear leucocytes from a patient with acute monocytic leukemia, were purified and characterized in regard to the molecular weights and kinetic properties. The molecular weights of TK 3 and TK 4 were 60 000 and 45 000, respectively. In the presence of 2 mM ATP, the molecular weight of TK 3 increased to 200 000, whereas the molecular weight of TK 4 was unchanged. Studies of the kinetic properties showed clear differences between TK 3 and TK 4. With thymidine as substrate, TK 3 showed biphasic kinetics with a Km of 22 microM, and TK 4 showed Michaelis-Menten kinetics with a Km of 0.33 microM. With ATP as substrate, TK 3 showed Michaelis-Menten kinetics with a Km of 100 microM, and TK 4 showed biphasic kinetics with a Km of 3.5 microM. With dTTP as inhibitor, TK 3 showed cooperative inhibition kinetics, and TK 4 showed non-cooperative competitive inhibition kinetics. The dTTP concentration at 50% inhibition was 75 microM for TK 3 but 380 microM for TK 4. Comparison of the molecular weights and the kinetic properties of TK 3 and TK 4 with the corresponding data previously obtained for TK 1 and TK 2 from normal human lymphocytes indicate the existence of four thymidine kinase isoenzymes in human leucocytes.
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PMID:Thymidine kinase isoenzymes in human acute monocytic leukemia. 385 34

New mutants of T4 have been isolated by using a strain of Escherichia coli lacking thymidine kinase activity. These T4 mutants, designated tk, are able to grow on this E. coli strain under light on plates containing 5-bromodeoxyuridine and were all found to be unable to induce thymidine kinase (ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21). All of these tk mutants fall into one complementation group which maps just to the right of rI on the standard T4 genetic map, far from most other genes coding for enzymes involved in pyrimidine metabolism. The tk mutants grow as well as wild-type T4, indicating that thymidine kinase is a non-essential enzyme.
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PMID:Isolation of mutants of bacteriophage T4 unable to induce thymidine kinase activity. 435 36

The activities of TdR kinase2 (ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21), AdR kinase (ATP: deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76), GdR kinase (ATP: deoxyguanosine 5'-phosphotransferase, without EC number), ATP (Mg2+)-ase (ATP phosphohydrolase, EC 3.6.1.3), nucleoside diphosphatase (nucleoside diphosphate phosphohydrolase, EC 3.6.1.6), nucleoside phosphotransferase (AMP: deoxynucleoside phosphotransferase, EC 2.7.1.77) and ribonucleotide 5'-diphosphate reductase (EC 1.17.4.1) were assayed in mitochondria of normal and regenerating rat liver. The activities of deoxynucleoside kinases are regulated: (a) by feedback inhibition of TdR kinase with dTTP and dCTP, and GdR kinase with dGTP; (b) GdR and AdR kinases by AdR and GdR inhibition, respectively; (c) by stimulation of GdR kinase with dTDP, dTTP and dATP. The stimulatory effects are correlated with changes of ATP (Mg2+)-ase and NDP-ase activities in regenerating liver mitochondria.
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PMID:Regulation of deoxynucleoside kinase activities in rat liver mitochondria. 612 3

The thymidine kinase-complex isolated from herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) is associated with the following enzyme activities:ATP:dThd (dCyd) deoxypyrimidine kinase, ATP:dTMP thymidylate kinase, ADP:dThd- and AMP:dThd 5'-phosphotransferase. In kinetic experiments it is shown that ara-AMP inhibits AMP:dThd- and ADP:dThd phosphotransferase activity, while acyclo-GMP impairs ADP:dThd phosphotransferase reaction only; the inhibition was found to be non-competitive. The functional subunit ATP:dThd kinase was not affected by either compound.
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PMID:Inhibition of the herpes simplex virus-coded thymidine kinase-complex by 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) and 9-(2-hydroxyethoxymethyl)guanine-monophosphate (acyclo-GMP). 620 25

Human fibroblast cytoplasmic thymidine kinase is stabilized by ATP. Sedimentation in sucrose gradients shows that in the presence of ATP, cytoplasmic thymidine kinase has a higher molecular weight (54 000) than in the absence of ATP (28 000). Removal of ATP by dialysis results in the loss of enzyme activity. The subsequent addition of ATP restores activity following a second order time course. These results are interpreted to indicate that in a human fibroblast cell line, transformed by SV40 virus, cytoplasmic thymidine kinase is a dimer in the presence of ATP, but a less active monomer in its absence. Mitochondrial thymidine kinase from the same cell line is not affected by ATP.
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PMID:Stabilization of SV40 transformed human fibroblast cytoplasmic thymidine kinase by ATP. 626 Nov 18


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