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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.
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
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