Structure of a type II thymidine kinase with bound dTTP.
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Birringer MS, Claus MT, Folkers G, Kloer DP, Schulz GE, Scapozza L
Structure of a type II thymidine kinase with bound dTTP.
FEBS Lett. 2005 Feb 28;579(6):1376-82.
- PubMed ID
- 15733844 [ View in PubMed]
- Abstract
The structure of human cytosolic thymidine kinase in complex with its feedback inhibitor 2'-deoxythymidine-5'-triphosphate was determined. This structure is the first representative of the type II thymidine kinases found in several pathogens. The structure deviates strongly from the known structures of type I thymidine kinases such as the Herpes simplex enzyme. It contains a zinc-binding domain with four cysteines complexing a structural zinc ion. Interestingly, the backbone atoms of the type II enzyme bind thymine via hydrogen-bonds, in contrast to type I, where side chains are involved. This results in a specificity difference exploited for antiviral therapy. The presented structure will foster the development of new drugs and prodrugs for numerous therapeutic applications.