Disease relevance of DTYMK

• In contrast, active human dTMP kinase can be expressed from the gene cloned into the baculovirus expression system, as evidenced by increased enzymatic activity by four- to five-fold [1].
• We have also examined four neuroblastoma cell lines for dTMP kinase mRNA levels and its kinase activities, which appear to vary according to cell growth rate [1].
• The nucleotide sequence of the cloned human cDNA is predicted to encode a 24 KD protein that shows considerable homology with the yeast and vaccinia virus dTMP kinase enzymes [2].
• Thymidylate kinase derived from the blast cells of human chronic myelocytic leukemia was purified 2186-fold to near homogeneity by means of alcohol precipitation, alumina-Cgamma gel fractionation, calcium phosphate gel fraction, ultrafiltration, and affinity column chromatography [3].
• Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway [4].

High impact information on DTYMK

• AZT monophosphate knocks thymidylate kinase for a loop [5].
• Phosphorylation of azidothymidine monophosphate to the diphosphate also appeared to be catalyzed by a host-cell enzyme, thymidylate kinase (EC 2.7.4.9) [6].
• These kinetic constants were consistent with the anabolism results and indicated that azidothymidine monophosphate is an alternative-substrate inhibitor of thymidylate kinase [6].
• 5. At 10(-8) M, the three antifolates had no effect on the activities of thymidylate synthetase, thymidine kinase, serine trans-hydroxymethylase, 5,10-methylenetetrahydrofolate dehydrogenase, 10-formyltetrahydrofolate synthetase, and thymidylate kinase [7].
• Mechanism studies show that zidovudine is phosphorylated to the monophosphate and diphosphate derivatives by the host cell cytosolic thymidine kinase and thymidylate kinase, respectively [8].

Chemical compound and disease context of DTYMK

• The identification of the human dTMP kinase gene and expression of its product in the baculovirus expression system should facilitate study of the mechanism of gene regulation and its role in pyrimidine metabolism [1].
• X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 A resolution [9].
• Human herpesvirus 8 open reading frame 21 is a thymidine and thymidylate kinase of narrow substrate specificity that efficiently phosphorylates zidovudine but not ganciclovir [10].
• The affinities of the monophosphates of 2'-fluoro-5-iodo-1-beta-D-arabinofuranosyluracil and its 5-methyl analog for cellular thymidylate kinase were two or more orders of magnitude greater than for the thymidine-thymidylate kinases from herpes simplex virus types 1 and 2 [11].
• These studies indicate that poor substrate acceptance of (E)-5-(2-bromovinyl)-2'-deoxyuridine monophosphate by herpes simplex virus type 2-specified thymidylate kinase is an important factor in situ in infected cells, preventing anabolism of the parent compound to its active triphosphorylated form [12].

Biological context of DTYMK

• Our results show the drastic effects that slight modifications of the substrates exert on the enzyme's conformation and, hence, activity and suggest the type of substitutions that are compatible with efficient phosphorylation by TMPK [13].
• The levels of dTMP kinase mRNA and its enzymatic activity fluctuate during the cell cycle, peaking at the S phase [1].
• Our results suggest that the expression of the dTMP kinase gene and its activity coincide with various stages of cell growth [1].
• Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth [1].
• Thymidylate kinase could utilize either ATP or dATP as an efficient phosphate donor, and showed substrate specificity for dTMP [14].

Anatomical context of DTYMK

• It was demonstrated that in this species, in contrast to a number of Acetabulariae, thymidylate kinase is translated on 70 S ribosomes [15].
• Therefore, it appears that low levels of thymidine phosphorylation suffice to fulfill the role of the viral enzyme in ganglia and that this role can be partially fulfilled by thymidylate kinase activity alone [16].
• We examined the effect of ethanol and a combination of ethanol and AZT on TK and TMPK activities in human Jurkat T cells [17].
• Inhibition of tumour growth is accompanied by a reduction of dThd, dGuo and dTMP kinase activities in tumour cytosol (by 91% and 74% and 55%, respectively) and decrease in contents of dTTP, dGTP and dATP (by 92%, 77% and 67%, respectively) in dNTP pool [18].

Associations of DTYMK with chemical compounds

• ADRT-MP has a low affinity toward thymidylate kinase (a Ki value of 28.9 microM versus a Km value of 0.56 microM for thymidylate), and toward thymidylate synthase (a Ki value of 180 microM versus a Km value of 8 microM for deoxyuridylate) [19].
• Human tissues contain a thymidylate kinase, a uridylate-cytidylate kinase, five isozymes of adenylate kinase, and several guanylate kinases [20].
• The anti-HIV analogue zidovudine (AZT) is phosphorylated by cytosolic thymidine kinase 1 (TK1), thymidylate kinase (dTMPK), and nucleoside diphosphate kinase [21].
• It was revealed that thymidylate kinase was purified together with cytosolic thymidine kinase from human term placenta by p-aminophenyl thymidine-3'-phosphate-CH-Sepharose affinity column chromatography, which has been commonly used for purification of thymidine kinase [14].
• From the observation that purified chloroplast preparations contained most of the dTMP kinase activity, and that chlorophyll and enzyme activity cosedimented in a linear sucrose gradient, it was concluded that the enzyme is located in the chloroplasts [22].

Other interactions of DTYMK

• In contrast, TS and TMK were not associated with prognosis [23].
• It is capable of phosphorylating deoxythymidine and deoxyuridine as does human thymidine kinase, deoxycytidine as does human deoxycytidine kinase, the cytosolic kinase whose amino acid sequence it most closely resembles, and thymidylate as does human thymidylate kinase [16].
• Silicon also has a role in synthesis of DNA, DNA polymerase and thymidylate kinase activity in diatoms [24].
• Two enzymes involved in the de novo synthesis of pyrimidines, orotic acid PRTase, and orotidine 5'-phosphate decarboxylase, were present in parasite extracts as were the enzymes for pyrimidine nucleotide phosphorylation: UMP-CMP kinase, dTMP kinase, nucleoside diphosphate kinase [25].

Analytical, diagnostic and therapeutic context of DTYMK

• Co-purification of thymidylate kinase and cytosolic thymidine kinase from human term placenta by affinity chromatography [14].
• In the presence of ATP, cytosolic thymidine kinase and thymidylate kinase could be separated from each other by Ultrogel AcA 34 filtration, and their molecular weights were estimated to be 70,000 and 50,000, respectively [14].
• The full stimulation of phosphorylation in nucleate and anucleate merogons eliminates any localization of the catalyzing enzymes (thymidine kinase and thymidylate kinase) in the maternal nucleus and other inner cytoplasmic contents differentially segregated by centrifugation [26].

References