Table 1.
Enzyme | Source-Gene | Subunit mass/Active form | Natural substrate | Prodrug | Variants/Mutants | Drug inhibitory action | References |
---|---|---|---|---|---|---|---|
| |||||||
Herpes Simplex Virus Thymidine Kinase (HSVTK) | Herpes Simplex Virus 1 (HSV-1) Thymidine Kinase (TK) | 45kDa homodimer | Thymidine | GCV, ACV | Mutant 30 | 1 | 52, 56–60 |
Mutant 75 | 1 | 52, 56, 58 | |||||
SR39 | 1 | 33, 58–65 | |||||
A168H | 1 | 66 | |||||
A167Y | 1 | 66, 69–72 | |||||
Q125N | 1, 2 | 68, 71, 72 | |||||
| |||||||
Bacterial Cytosine Deaminase (bCD) | Escherichia coli –codA | 48kDa homohexamer | Cytosine | 5-FC | D314 mutants | 1, 2, 4 | 31, 34, 44, 74, 79 |
bCD1525 | 1, 2, 4 | 31 | |||||
| |||||||
Yeast Cytosine Deaminase (yCD) | Saccharomyces cerevisiae –fcy1 | 18kDa homodimer | Cytosine | 5-FC | yCD triple | 1, 2, 4 | 32, 81 |
D92E | 1, 2, 4 | 32 | |||||
| |||||||
Drosophila melanogaster Deoxynucleoside Kinase (Dm-dNK) | Drosophilamelanogaster –dNK | 29kDa hom | All four deo | AZT, ddC | MuD | 1, 5 | 84–86 |
CdA | B5 | 1 | 85, 87 | ||||
F-AraA | B10 | 1, 3 | 85 | ||||
GCV, AraG | M88R | 1 | 87–90 | ||||
D4T | HDHD-12, HD-16 | 1, 5 | 91 | ||||
ddT | R4.V3 | 1 | 92 | ||||
| |||||||
Deoxycytidine Kinase (dCK) | Homo sapiens –dCK | 30.5kDa homodimer | Deoxycytidine | dFdC, AraC, L-dT | DMMA, DMLA | 1, 3 | 100 |
AZT | EpTK6 | 1, 3, 5 | 101 | ||||
dFdC, AraC | Ser-74 | 1, 3 | 102, 103 | ||||
| |||||||
Purine Nucleoside Phosphorylase (PNP) | Escherichia coli -deoD | 150kDa homodimer | Purine ribonucleosides | Me(talo)-MeP-R | M64V | 1, 4 | 115, 117, 118 |
1. DNA synthesis
2. Thymidylate synthetase
3. Ribonucleotide reductase
4. RNA/protein synthesis
5. Reverse transcriptase