Disease relevance of tdk

• This genetic complementation assay was used in concert with subcloning procedures to identify the minimal region (a 900 bp EcoRI-SalI fragment) which contained the E. coli thymidine kinase gene (tdk) [1].
• Using lambda bacteriophage clones from the Kohara Escherichia coli library spanning minutes 25.5 to 28.5 on the E. coli chromosome (strain W3110), two overlapping DNA fragments were identified which were able to confer thymidine kinase (TK) enzyme activity to a TK- strain of E. coli (KY895) [1].
• Using a distance matrix method, the evolutionary relationships among the TK aa sequence of poxviruses, eukaryotes and prokaryotes were analyzed and a potential phylogenetic tree was established [2].
• The E. coli amino acid (aa) sequence showed significant similarity to the corresponding TK polypeptides of vertebrates and large DNA viruses, but showed no similarity to known herpes virus TK enzymes [2].
• They are based on two genes for the resistance to Blasticidin S (BlaS) and on the thymidine kinase (Tk) gene of herpes simplex virus (HSV) [3].

High impact information on tdk

• New positive/negative selectable markers for mammalian cells on the basis of Blasticidin deaminase-thymidine kinase fusions [3].
• This places the tdk gene at approximately minute 27.35 on the E. coli W3110 chromosome, about 15 kb downstream from the narG locus and approximately 25 kb upstream of the trp operon [1].
• Nucleotide sequence of the Escherichia coli thymidine kinase gene provides evidence for conservation of functional domains and quaternary structure [1].
• Although the predicted Mr of the E. coli TK protein was 23.5 kDa, gel-filtration analyses suggested that, like eukaryotic thymidine kinases, the active form of this enzyme is a multimeric complex.(ABSTRACT TRUNCATED AT 250 WORDS)[1]
• Since the thymidine kinase (TK) activity of herpesviruses has been associated with virulence, inactivation of the encoding gene in the ILTV genome should attenuate the virus [4].

Biological context of tdk

• The affected gene maps near 26 min between chl C and tdk on the chromosome of the organism [5].
• In order to prevent reversion and also to enable identification of the modified virus, a "marker" transcriptional unit (Escherichia coli lacZ gene fused to a SV-40 3'-polyadenylation signal sequence and regulated by the pseudorabies virus gX gene promoter) was inserted via homologous recombination at one of two loci within the ILTV TK gene [4].
• The thymidine kinase gene from B. anthracis Sterne strain (34F2) (Ba-TK) was cloned and expressed in E. coli, and the product was purified and characterized regarding its substrate specificity [6].

Associations of tdk with chemical compounds

• Assays of key regulatory enzymes in de novo pyrimidine synthesis (uridine monophosphate synthase) and salvage biochemistry (thymidine kinase) confirmed that FOA resistance in for1-1/for1-1 plants was not due to altered enzymatic activities [7].

Analytical, diagnostic and therapeutic context of tdk

• Nucleoside analogs are well-known antiviral and anticancer prodrugs, and thymidine kinase catalyzes the rate-limiting step in the activation of pyrimidine nucleoside analogs used in chemotherapy [6].

References