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)

On the basis of their restriction endonuclease digestion patterns, four Australian bovine herpesvirus type 1 (BHV-1) isolates were classified as belonging to the BHV-1.2a subtypes. The thymidine kinase (TK) genes of all four BHV-1.2a isolates were located on a 3.5 kb SalI restriction fragment. This is in contrast to North American and European BHV-1.1 isolates whose TK genes are contained on a 2.6 to 2.8 kb SalI fragment. The restriction fragments containing the TK genes were cloned into phagemid vectors and their sequences determined using the dideoxynucleotide chain termination method. The BHV-1.2a isolates possessed identical TK gene sequences, which differed from previously published TK sequences for the LA and 6660 BHV-1.1 strains. In addition to five single base alterations, there were six separate base insertions which resulted in two major frameshifts which spanned an area of 72 amino acids or 20% of the expressed TK gene product. The predicted amino acid sequence exhibited a higher degree of similarity to other herpesvirus TKs, suggesting that previously published TK gene sequences may have been incorrect. The present nucleotide sequence and corresponding amino acid composition reinforces previous observations concerning regions of herpesvirus TK amino acid conservation and should assist in future studies into the evolution and functional domains of herpesvirus TKs.
J Gen Virol 1990 Oct
PMID:The location and nucleotide sequence of the thymidine kinase gene of bovine herpesvirus type 1.2. 217 55

Mycobacterium microti incorporated a wide range of exogenously supplied pyrimidines into its nucleic acids. M. avium incorporated a relatively narrow range of pyrimidines but both M. avium and M. microti when recovered after growth in vivo incorporated a slightly wider range of pyrimidines than the same strains grown in vitro. M. microti and M. leprae could not take up uridine nucleotides directly but could utilize the pyrimidines by hydrolysing them to uridine and then taking up the uridine. Pyrimidine biosynthesis, judged by the ability to incorporate carbon from CO2 or aspartate into pyrimidines was readily detected in non-growing suspensions of M. microti and M. avium harvested from Dubos medium, which does not contain pyrimidines. The biosynthetic activity was diminished in mycobacteria grown in vivo when there is likely to be a source of pyrimidines which they might use. Relative activities for pyrimidine biosynthesis de novo in M. microti were 100 for cells isolated from Dubos medium, 6 for cells isolated from Dubos medium containing the pyrimidine cytidine and 11 from cells recovered after growth in mice. In contrast, relative activities for a scavenging reaction, uracil incorporation, were 100, 71 and 59, respectively. Three key enzymes in the pathway of pyrimidine biosynthesis de novo were detected in M. microti and M. avium. Two, dihydroorotate synthase and orotate phosphoribosyltransferase appeared to be constitutive in M. microti and M. avium. Aspartate transcarbamoylase activity was higher in these mycobacteria grown in vivo than in Dubos medium but it was repressed in M. microti or M. avium grown in Dubos medium in the presence of 50 microM-pyrimidine. Aspartate transcarbamoylase was strongly inhibited by the feedback inhibitors ATP, CTP and UTP. Enzymes for scavenging pyrimidines were detected at low specific activities in all mycobacteria studied. Activities of phosphoribosyltransferases, enzymes that convert bases directly to nucleotides, were not related to the ability of intact mycobacteria to take up pyrimidine bases while activities of pyrimidine nucleoside kinases were generally related to the ability of intact mycobacteria to take up nucleosides. Phosphoribosyltransferase activity for uracil, cytosine, orotic acid and--in organisms grown in Dubos medium with 50 microM-uridine-thymine, as well as kinases for uridine, deoxyuridine, cytidine and thymidine were detected in M. microti. However, M. avium only contained uracil and orotate phosphoribosyltransferase, uridine, cytidine and thymidine kinase, and additionally deoxyuridine kinase when grown axenically with 50 microM-uracil, reflecting its more limited abilities in pyrimidine scavenging.
J Gen Microbiol 1990 Jan
PMID:Biosynthesis and scavenging of pyrimidines by pathogenic mycobacteria. 219 Oct 77

A murine model based on infection by the respiratory route has been used to study the pathogenesis of recombinant vaccinia viruses. The neurovirulent Western Reserve (WR) strain and the Wyeth smallpox vaccine strain were used as vectors. Recombinant viruses were constructed by insertion of the Epstein-Barr virus membrane glycoprotein 340 gene into the thymidine kinase (TK) gene of each vaccinia virus. Intranasal inoculation of DBA/2 mice with 10(6) pock-forming units (pk.f.u.) of the WR strain was lethal but mice survived similar infection with the WR recombinant virus. Each virus was recovered from lung, blood and brain but, unlike wild-type virus, the recombinant virus was subsequently cleared. No deaths occurred after similar infection with the Wyeth strain or the Wyeth recombinant virus. There was limited growth of the Wyeth strain in the respiratory tract, low levels of virus in the blood and only sporadic recovery in brain extracts. The Wyeth recombinant virus was cleared rapidly with little viraemia or detectable infection of the central nervous system. No phenotypic character determined in vitro could be related consistently to the virulence of wild-type and recombinant viruses. Although the lethal character of the WR strain was affected by its TK+ phenotype, mice survived infection by intranasal inoculation with 10(6) pk.f.u. of WR TK+ recombinant viruses which either expressed the human interleukin 2 gene or had a deficient vaccinia virus growth factor gene.
J Gen Virol 1990 Nov
PMID:Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route. 225 56

We have determined the genomic location and nucleotide sequence of the equine herpesvirus 4 thymidine kinase (TK) gene. The gene is positioned at approximately 0.48 map units within the long unique component of the genome and is flanked by genes encoding a herpes simplex virus 1 (HSV-1) UL24 homologue and glycoprotein H. The predicted protein is composed of 352 amino acids, has an Mr of 38,800 and exhibits 36% identity to the predicted TK of HSV-1.
J Gen Virol 1990 Aug
PMID:The nucleotide sequence of the equine herpesvirus 4 thymidine kinase gene. 239

cDNA molecules encoding the structural proteins of the virulent Trinidad donkey and the TC-83 vaccine strains of Venezuelan equine encephalitis (VEE) virus were inserted under control of the vaccinia virus 7.5K promoter into the thymidine kinase gene of vaccinia virus. Synthesis of the capsid protein and glycoproteins E2 and E1 of VEE virus was demonstrated by immunoblotting of lysates of CV-1 cells infected with recombinant vaccinia/VEE viruses. VEE glycoproteins were detected in recombinant virus-infected cells by fluorescent antibody (FA) analysis performed with a panel of VEE-specific monoclonal antibodies. Seven E2-specific epitopes and two of four E1-specific epitopes were demonstrated by FA.
J Gen Virol 1988 Dec
PMID:Recombinant vaccinia/Venezuelan equine encephalitis (VEE) virus expresses VEE structural proteins. 246 13

We constructed a recombinant herpes simplex virus (HSV) containing the transcribed coding and non-coding sequences of HSV-1 strain F glycoprotein B (gB) gene, a gamma 1 gene, fused to the promoter-regulatory sequences of the HSV-1 alpha 4 gene and inserted into the thymidine kinase gene of RH1G44, an HSV-1 x HSV-2 recombinant that contains an HSV-2 gB gene at the natural locus. Phenotypic analyses of the insertion mutant, R3145, showed that the alpha gB gene was transcribed in the presence of cycloheximide but underwent partial conversion to the HSV-2 form. Nucleotide sequencing of the gene indicated that the 5' crossover occurred between nucleotides 107 and 117 upstream from the translation initiation site and that the 3' crossover occurred between the sequences specifying amino acids 402 and 412 of the HSV-1 gB. The chimeric protein consisted of an N-terminal 405 to 415 amino acids encoded by the HSV-2 gene and a C-terminal 462 to 472 amino acids encoded by the HSV-1 gene. Comparison of the reactivity of the parental and recombinant gB with type-specific monoclonal antibodies indicated that the chimeric gB lost reactivity with four HSV-1-specific antibodies but gained reactivity with three HSV-2-specific antibodies.
J Gen Virol 1989 Mar
PMID:A subset of type-specific epitopes map in the amino terminus of herpes simplex virus type 1 glycoprotein B. 247 97

We have constructed recombinant human adenovirus (Ad) vectors containing the glycoprotein gene of vesicular stomatitis virus (VSV). The structural gene of the VSV glycoprotein was modified by the addition of promoter and poly(A) addition sequences from the herpes simplex virus type 1 thymidine kinase (TK) gene and inserted, in either orientation, into early region 3 (E3) of human Ad type 5. The recombinant vectors were fully infectious and replicated in HeLa cells in culture. The TK promoter was functional in both insert orientations and responsive to trans-activation by herpes virus infection; however production of VSV glycoprotein in readily detectable amounts was only obtained with the vector having an insert in the E3 parallel orientation (AdG12), and depended principally on transcripts initiating within upstream Ad sequences. The onset of expression of the glycoprotein in AdG12-infected cells was detectable at about the same time as the Ad 72K DNA-binding protein encoded by E2, and its synthesis was not prevented by blocking viral DNA synthesis. The VSV glycoprotein produced by AdG12 was fully processed and could function to direct low pH-induced fusion of infected cells. These Ad vectors have considerable potential utility for the expression of antigens in cell culture and for the immunization of animals in studies of immunity and protection.
J Gen Virol 1989 Feb
PMID:Expression of the glycoprotein of vesicular stomatitis virus by infectious adenovirus vectors. 254 46

A genetically engineered herpes simplex virus type 1 (HSV-1)thymidine kinase (TK) deletion mutant has been constructed and used to investigate the role of this gene in pathogenesis. Inoculation of mice with the HSV TK deletion mutant resulted in the establishment of latent ganglionic infection as demonstrated by superinfection of explanted ganglia with wild-type (wt) virus but not by routine explant culture suggesting that the virus-encoded TK is not essential for the establishment of latent infection but may be necessary for either reactivation or virus replication following reactivation. In addition, Southern blot hybridization has been used to demonstrate in vivo complementation of this mutant by wt virus in both peripheral and central nervous system tissues of mice during acute infection and to show that such complementation can result in the establishment and reactivation of latent TK- infection.
J Gen Virol 1989 Apr
PMID:The role of herpes simplex virus type 1 thymidine kinase in pathogenesis. 254 63

Five thymidine kinase (TK)-deficient mutants (B1 to B5) of bovine herpesvirus type 1 (BHV-1) were isolated by selection for resistance to the nucleotide analogue bromovinyldeoxyuridine. The genetic lesion in mutant B1 was localized in a 2.7 kb SalI-SalI subfragment (fTK2.7) which maps between 0.456 and 0.475 within the HindIII A fragment of the BHV-1 genome. The tk genes from wild-type and the TK-mutants B1 to B5 were cloned and sequenced using eight unique synthetic primers designed from a published sequence. The BHV-1 tk gene sequence for the strain 6660 contained some differences compared with that published previously for strain LA. Alignment of the predicted amino acid sequence of the BHV-1 TK polypeptide with different herpesvirus TKs revealed five strongly conserved regions and also identified putative functional relationships with other enzymes. Several interesting features were apparent in the tk gene sequences from the TK- mutants. The TK mutant B1 was a typical frameshift and chain termination mutant due to the deletion of a single base. The tk gene sequence of mutant B2 revealed the deletion of three bases resulting in the loss of valine at amino acid residue 174 of the TK polypeptide. The tk genes of mutants B3 to B5 contained an identical change of a single base addition resulting in frameshift and premature chain termination. In contrast to wild-type BHV-1, the TK-defective mutants were incapable of adsorbing TK-neutralizing antibodies from serum.
J Gen Virol 1989 Apr
PMID:Analysis of the bovine herpesvirus type 1 thymidine kinase (TK) gene from wild-type virus and TK-deficient mutants. 254 66

We present the nucleotide sequence of a region from the genome of the A + T-rich gammaherpesvirus, herpesvirus saimiri (HVS), which includes the coding sequences for the viral thymidine kinase (TK) gene. The organization of genes in this region resembles the homologous region of the Epstein-Barr virus (EBV) genome and is very compact, using overlapping coding sequences and with nucleotides shared by initiation and termination codons of neighbouring reading frames. The HVS TK is predicted to contain a 527 residue polypeptide with the first part of the presumptive nucleotide-binding site [(L, I, V)(F, Y)(I, L)(D, E)(G)(X)(X)(G)(L, I, V, M)(G)(K)(T, S)(T, S)] located at residues 212 to 224. This motif is close to the amino terminus of the TK polypeptides of alphaherpesviruses and the polypeptides of the cellular and poxvirus-encoded enzymes. The corresponding reading frame of the human gammaherpesvirus (EBV) also has a long amino-terminal extension but significant amino acid sequence similarities between the HVS and EBV sequences are not observed until the region of the nucleotide-binding site. Comparisons of these homologous carboxy-terminal sequences of the HVS- and EBV-encoded proteins with those from six alphaherpes viruses and proteins encoded by Marek's disease virus (MDV) and the herpesvirus of turkeys (HVT) confirm that the HVS and EBV sequences are products of a distinct lineage. The sequences of alphaherpesvirus enzymes than to those of HVS and EBV. Comparison of these 10 highly divergent TK sequences extends and refines the identification of essential features of this family of herpesvirus enzymes and defines 19 positions at which all sequences have identical residues.
J Gen Virol 1989 Nov
PMID:A comparative analysis of the sequence of the thymidine kinase gene of a gammaherpesvirus, herpesvirus saimiri. 255 34


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