Interaction of the Recombinant Herpes Simplex Virus Type 1 Thymidine Kinase with Thymidine and Aciclovir: A Kinetic Study
Susanna Kussmann‐Gerber, Christine Wurth, Léonardo Scapozza, Beatrice Pilger, V. Pliška, Gerd Folkers
Abstract
Susanna Kussmann‐Gerber, Christine Wurth, Léonardo Scapozza, Beatrice Pilger, V. Pliška, Gerd Folkers
Abstract
Herpes Simplex Virus type 1 thymidine kinase (HSV 1 TK) is a key target for antiviral therapy and it phosphorylates a broad spectrum of nucleosides and nucleotides. We report the results from kinetic and inhibition experiments with HSV 1 TK, and show that there is a preferred, but not exclusive, binding order of substrates, i.e. dT binds prior to ATP. Furthermore, the results provide new informations on the mechanism of binding suggesting that HSV1 TK undergoes conformational changes during the catalytic cycle.
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Herpes Simplex Virus type 1 thymidine kinase (HSV 1 TK) is a key target for antiviral therapy and it phosphorylates a broad spectrum of nucleosides and nucleotides. We report the results from kinetic and inhibition experiments with HSV 1 TK, and show that there is a preferred, but not exclusive, binding order of substrates, i.e. dT binds prior to ATP. Furthermore, the results provide new informations on the mechanism of binding suggesting that HSV1 TK undergoes conformational changes during the catalytic cycle.
Key concepts: Thymidine kinase, Aciclovir, Herpes simplex virus, Thymidine, Recombinant DNA, Virology, Chemistry, Nucleotide