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Herpes simplex virus 1 thymidine kinase (HSV-1 TK)

Target
HSV-1 TK
Molecular classification
Enzyme
01

Overview

Herpes simplex virus 1 thymidine kinase is a viral enzyme (encoded by UL23 gene, 376 amino acids) that catalyzes the phosphorylation of deoxythymidine (dT) to deoxythymidine monophosphate (dTMP) using ATP in the nucleoside salvage pathway, as well as phosphorylating a broad range of nucleoside analogs. It is a homodimeric α/β protein with a conserved active site including a glycine-rich P-loop for ATP binding and substrate-specific pockets, showing structural homology to nucleoside monophosphate kinases but with additional peptide segments. Unlike narrow-specificity human TK1, HSV-1 TK enables activation of antivirals like acyclovir and ganciclovir, making it a key therapeutic target in anti-herpesvirus therapy and suicide gene therapy for cancer, where its expression sensitizes cells to prodrug-induced cell death.

Other names
Thymidine kinase from herpes simplex virus type 1HSV1-TKTKHSV1Viral thymidine kinase
02

Mechanism of action

Phosphorylation of prodrugs (e.g., GCV, ACV) to active triphosphate forms that inhibit viral DNA polymerase\nSelective activation in virus-infected or transgene-expressing cells for antiviral or suicide gene therapy

03

Biological functions

Nucleoside salvage pathway (phosphorylation of thymidine to dTMP)Phosphorylation of nucleoside analogs
04

Disease associations

Infection (herpes simplex virus replication and latency)Cancer (suicide gene therapy for tumor ablation)
05

Safety considerations

Immunogenicity of HSV-1 TK in gene therapy applicationsPotential immunosuppression from high-dose GCV requiring enzyme optimization
06

Interacting drugs

Ganciclovir (GCV)

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