We have partially purified suid pseudorabies virus (PRV) thymidine kinase from infected thymidine kinase- mouse cells, and cytosolic swine thymidine kinase from lymphatic glands, and we have found that PRV thymidine kinase, unlike the host enzyme, shows no stereospecificity for D- and L-beta-nucleosides. In vitro, unnatural L-enantiomers, except L-deoxycytidine, function as specific inhibitors for the viral enzyme in the order: L-thymidine >> L-deoxyguanosine > L-deoxyuridine > L-deoxyadenosine. Contrary to human and swine thymidine kinases and like herpes simplex virus-1 and -2 thymidine kinases, PRV thymidine kinase phosphorylates both the natural (D-) and the unnatural (L-) thymidine enantiomers to their corresponding monophosphates with comparable efficiency. The kinetic parameters Vmax/Km for D- and L-thymidine are 3.7 and 2.3 respectively. Our results demonstrate that the lack of stereospecificity might be a common feature of the thymidine kinases that are encoded by human and animal herpes viruses. These observations could lead to the development of a novel class of antiviral drugs.
Lack of stereospecificity of suid pseudorabies virus thymidine kinase
- Views Icon Views
- PDF LinkPDF
- Share Icon Share
- Cite Icon Cite
G Maga, A Verri, L Bonizzi, W Ponti, G Poli, A Garbesi, D Niccolai, S Spadari, F Focher; Lack of stereospecificity of suid pseudorabies virus thymidine kinase. Biochem J 1 September 1993; 294 (2): 381–385. doi: https://doi.org/10.1042/bj2940381
Download citation file: