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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)

Herpes simplex virus (HSV) type 1 can be differentiated from HSV type 2 on the basis of the sensitivity to 2'-deoxythymidine-5'-monophosphate of thymidine kinase induced in primary rabbit kidney cells. Whereas thymidine kinase induced by five strains of HSV type 1 (TK 1) is stimulated by suitable concentrations of 2'-deoxythymidine-5'-monophosphate, thymidine kinase induced by eight strains of HSV type 2 (TK 2) is inhibited. On the other hand, TK 2 is strongly inhibited by 2'-deoxythymidine-5'-triphosphate and by 2-bromo-2'-deoxyuridine-5'-triphosphate. The investigation of TK induced by six freshly isolated strains of HSV cross-reacting in neutralisation tests revealed two strains which induced TK 1 and two strains which induced TK 2. Two other strains induced thymidine kinase, the activity of which under the influence of these thymidine analogues was between that of TK 1 and TK 2. The properties of thymidine kinase remained constant after cloning the virus and thus is a genetically fixed trait due to recombination which could well occur in vivo.
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PMID:Biochemical classification of herpes simplex virus types 1 and 2, and of intermediate strains on the basis of different susceptibilities of thymidine kinase to thymidine analogues. 0 38

In an attempt to differentiate between thymidine kinase (EC.2.4.1.21) induced by herpesvirus hominis type I (TK I) and type 2 (TK2), the different susceptibilities to the modifying effects of some thymidine analogues proved to be useful criteria: (I)2'-deoxythymidine-5'-triphosphate (dThd-5'-PPP) inhibits TK 2 at a concentration of 0-125 mM by 90%, whereas TK I is inhibited at 4-03 mM by 50%. (2) 2'-deoxythymidine-5'-monophosphate (dThd-5'-P) competitively inhibits TK 2 at all concentrations tested. On the other hand, the direction of its effect on TK I is concentration dependent: at 500 mum it stimulates and at 8 mM inhibits TK I activity. During enzyme kinetic studies, TK I displays substrate inhibition which is reversed by dThd-5'-P. This result explains the stimulating effect of dThd-5'-P at 500 muM. This phenomenon suggests the existence on the enzyme molecule of a second binding site for dThd which mediates substrate inhibition and which can be occupied also by dThd-5'-P. After polyacrylamide gel electrophoresis of TK I, the stimulation by dThd-5'-P disappears, suggesting the separation of the second binding site from the catalytic centre.
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PMID:Regulation by thymidine monophosphate and other nucleotides of thymidine kinase activity in extracts from primary rabbit kidney cells infected by HSV types 1 and 2. 17 38

In six patients with untreated, chronic myelocytic leukemia (CML), the dominating thymidine kinase (TK) activity was compared with the fetal form, TK 1, from mitogen stimulated and the adult form TK 2 from unstimulated normal human lymphocytes, and with TK-1-onc, TK-3-onc and TK-4-onc. This was done in human acute, myelocytic and monocytic leukemias, using the combined thymidine/dTTP enzyme kinetics for isoenzyme characterization. TK-1-onc was found in one, TK-2-onc in two and TK-3-onc in three CML patients. The suffix -onc indicates the difference in ATP kinetics and molecular weights between the normal and the leukemic thymidine kinases. A possible relation between the isoenzyme forms and the types of leukemias is discussed.
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PMID:Thymidine kinase in human leukemia--expression of three isoenzyme variants in six patients with chronic myelocytic leukemia. 230 55

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 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

The two thymidine kinases, TK 1 and TK 2, found in phytohemagglutinin-stimulated human lymphocytes and the thymidine kinase, TK 2N, found in unstimulated human lymphocytes were purified and characterized. All three kinases had molecular weights between 70 000 and 75 000 which increased to 170 000-200 000 in the presence of 2 mM ATP. Studies on the kinetic properties of the enzymes with thymidine and ATP as the substrates and dTTP as the inhibitor showed clear differences between TK 1 and TK 2, but a close similarity between TK 2 and TK 2N. With thymidine as the variable substrate, TK 1 showed Michaelis-Menten kinetics, whereas TK 2 and TK 2N showed characteristic biphasic kinetics. With ATP as the variable substrate, all three enzymes showed positive cooperative kinetics, but TK 2 and TK 2N lost the cooperativity in the presence of dTTP. The results from inhibition studies showed, that dTTP was a cooperative inhibitor of TK 1 but a non-cooperative inhibitor of TK 2 and TK 2N.
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PMID:Differences in the kinetic properties of thymidine kinase isoenzymes in unstimulated and phytohemagglutinin-stimulated human lymphocytes. 650 22