Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases.

PCR detection of thymidine kinase gen of latent herpes simplex Virus type 1 in mice trigeminal ganglia

  Herpes simplex virus type 1 establishes a latent infection in the peripheral nervous system following primary infection. During latent infection, virus genome exhibit limited transcription, with the HSV LATs consistently detected in latency infected ganaglia. Following ocular infection viral latency develops in the trigeminal ganglia. In this study PCR has been used for detection of HSV-1 nuc...

Restriction Enzyme Analysis of Thymidine Kinase Gene in Four Iranian Isolates of Herpes Simplex Virus Type 1

Kinetic studies of herpes simplex virus type 1-encoded thymidine and thymidylate kinase, a multifunctional enzyme.

Kinetic studies of the reactions catalyzed by herpes simplex virus type l-encoded thymidine and thymidylate multifunctional kinase indicate that the addition of substrates (thymidine and ATP*Mg’+, or thymidylate and ATP l Mg2+) to the enzyme is random, while release of the products (thymidylate and ADP*M8+, or thymidine diphosphate and ADP*Mg+) is ordered, with ADP.Mg2+ being released first. Th...

Mutation of Gln125 to Asn selectively abolishes the thymidylate kinase activity of herpes simplex virus type 1 thymidine kinase.

The broad substrate specificity of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) has provided the basis for selective antiherpetic therapy and, more recently, suicide gene therapy for the treatment of cancer. We have now constructed an HSV-1 TK mutant enzyme, in which an asparagine (N) residue is substituted for glutamine (Q) at position 125, and have evaluated the effect of this am...

Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy.

Unlike most DNA viruses, poxviruses replicate in the cytoplasm of host cells. They encode enzymes needed for genome replication and transcription, including their own thymidine and thymidylate kinases. Some herpes viruses encode only 1 enzyme catalyzing both reactions, a peculiarity used for prodrug activation to obtain maximum specificity. We have solved the crystal structures of vaccinia viru...