EC Number |
Protein Variants |
Reference |
---|
2.7.4.9 | D90L |
high similarity to the wild-type. Less than 10% of wild-type activity |
-, 758591 |
2.7.4.9 | F105Y |
increase in activity and preferential specificity towards 3'-azido-3'-deoxythymidine 5'-monophosphate |
693440 |
2.7.4.9 | F105Y |
stabilization of active site dynamics leads to increased activity with 3-azido-3-deoxythymidine monophosphate for the mutant enzyme |
758582 |
2.7.4.9 | F74A |
mutant enzyme has no enzymatic activity |
-, 758812 |
2.7.4.9 | G146A |
mutation is accompanied by a small but significant enhancement of the thermodynamic stability, midpoint denaturation temperature is 3°C higher than that of the wild-type enzyme, midpoint transition is 3.3 M urea, compared to 3.0 M for the wild-type enzyme |
645202 |
2.7.4.9 | K16M |
high similarity to the wild-type. Less than 10% of wild-type activity |
-, 758591 |
2.7.4.9 | more |
engineering of enzyme/prodrug combinations for selectively inducing apoptosis in lentiviral vector-transduced cells, based on designed variants of human thymidylate kinase that effectively phosphorylate 3'-azido-3'-deoxythymidine. Recombinant lentiviral vector constructs contain either mutant F105Y of human thymidylate kinase or mutant R16G that additionally displays an exchange of 11 amino acids residues of wild-type with 13 residues from the Escherichia coli orthologue. In addition, they contain human CD19 lacking its cytoplasmic tail |
694282 |
2.7.4.9 | more |
expression as fusion protein with Green Fluorescent Protein in HeLa cell, mitochondrial localization. Over-expression of TMPK2 increases the steady-state level of cellular dTTP and promotes the conversion of radioactive labeled-thymidine and -dTMP to dTDP and dTTP in mitochondria |
692491 |
2.7.4.9 | more |
introduction of an engineered, highly active dTMP kinase into T cells for more efficient conversion of the 3'-azido-3'-deoxythymidine prodrug to its diphosphorylated form and blocking replication of formerly 3'-azido-3'-deoxythymidine resistant HIV. Substitution of the LID domain in human enzyme by the Escherichia coli LID sequence and mutation of the P-loop Arg residue to Gly results in 100fold higher rate of 3'-azido-3'-deoxythymidine monophosphate phosphorylation than the native form. Link of mutant enzymes to the protein transduction domain of Tat for direct cell delivery |
693440 |
2.7.4.9 | more |
silencing of expression in p53-/- and in p53+/+ colon cancer cells by lentiviral-based small hairpin RNA results in decrease of the dTTP pool without affecting p53 expression and generating cytotoxicity. Thymidylate kinase knock-down increases doxorubicin sensitivity dramatically in p53-proficient, p53-null HCT-116,and LoVo colon cancer cells. The decrease in the dTTP pool augments the DNA damage response and enhances apoptotic induction after exposure to low-dose doxorubicin, leading to cell death |
691610 |