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Literature summary for 2.7.4.9 extracted from

  • Lavie, A.; Su, Y.; Ghassemi, M.; Novak, R.M.; Caffrey, M.; Sekulic, N.; Monnerjahn, C.; Konrad, M.; Cook, J.L.
    Restoration of the antiviral activity of 3'-azido-3'-deoxythymidine (AZT) against AZT-resistant human immunodeficiency virus by delivery of engineered thymidylate kinase to T cells (2008), J. Gen. Virol., 89, 1672-1679.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.4.9

Application

Application Comment Organism
medicine 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. Combined treatment of HIV-infected T-cells with 3'-azido-3'-deoxythymidine and the engineered thymidylate kinases restores 3'-azido-3'-deoxythymidine-induced repression of viral production Escherichia coli
medicine 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. Combined treatment of HIV-infected T-cells with 3'-azido-3'-deoxythymidine and the engineered thymidylate kinases restores 3'-azido-3'-deoxythymidine-induced repression of viral production Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
-
 Escherichia coli
-
 Homo sapiens

Protein Variants

Protein Variants Comment Organism
F105Y increase in activity and preferential specificity towards 3'-azido-3'-deoxythymidine 5'-monophosphate Homo sapiens
additional information 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 Escherichia coli
additional information 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 Homo sapiens

Organism

Organism UniProt Comment Textmining
Escherichia coli
-
-
-
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 3'-azido-3'-deoxythymidine 5'-monophosphate i.e. AZT Homo sapiens ADP + 3'-azido-3'-deoxythymidine 5'-diphosphate
-
 ?
ATP + dTMP
-
 Homo sapiens ADP + dTDP
-
 ?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.003
-
 3'-azido-3'-deoxythymidine 5'-monophosphate wild-type enzyme fused to the protein transduction domain of Tat Homo sapiens
0.012
-
 3'-azido-3'-deoxythymidine 5'-monophosphate wild-type Homo sapiens
0.14
-
 dTMP mutant F105Y fused to the protein transduction domain of Tat Homo sapiens
0.17
-
 dTMP mutant F105Y Homo sapiens
0.17
-
 3'-azido-3'-deoxythymidine 5'-monophosphate mutant F105Y fused to the protein transduction domain of Tat Homo sapiens
0.27
-
 3'-azido-3'-deoxythymidine 5'-monophosphate mutant F105Y Homo sapiens
0.73
-
 dTMP wild-type Homo sapiens
0.76
-
 dTMP wild-type enzyme fused to the protein transduction domain of Tat Homo sapiens
0.83
-
 dTMP mutant carrying a substitution of the LID domain in human enzyme by the Escherichia coli LID sequence and mutation of the P-loop Arg residue to Gly and fused to the protein transduction domain of Tat Homo sapiens
1.1
-
 dTMP mutant carrying a substitution of the LID domain in human enzyme by the Escherichia coli LID sequence and mutation of the P-loop Arg residue to Gly Homo sapiens
1.5
-
 3'-azido-3'-deoxythymidine 5'-monophosphate mutant carrying a substitution of the LID domain in human enzyme by the Escherichia coli LID sequence and mutation of the P-loop Arg residue to Gly and fused to the protein transduction domain of Tat Homo sapiens
1.7
-
 3'-azido-3'-deoxythymidine 5'-monophosphate mutant carrying a substitution of the LID domain in human enzyme by the Escherichia coli LID sequence and mutation of the P-loop Arg residue to Gly Homo sapiens