Structural Basis for the Dual Thymidine and Thymidylate Kinase Activity of Herpes Thymidine Kinases
Copyright policy )Structural Basis for the Dual Thymidine and Thymidylate Kinase Activity of Herpes Thymidine Kinases
Crystal structures of equine herpesvirus type-4 thymidine kinase (EHV4-TK) in complex with (i). thymidine and ADP, (ii). thymidine and SO(4) and the bisubstrate analogs, (iii). TP(4)A, and (iv). TP(5)A have been solved. Additionally, the structure of herpes simplex virus type-1 thymidine kinase (HSV1-TK) in complex with TP(5)A has been determined. These are the first structures of nucleoside kinases revealing conformational transitions upon binding of bisubstrate analogs. The structural basis for the dual thymidine and thymidylate kinase activity of these TKs is elucidated. While the active sites of HSV1-TK and EHV4-TK resemble one another, notable differences are observed in the Lid regions and in the way the enzymes bind the base of the phosphoryl-acceptor. The latter difference could partly explain the higher activity of EHV4-TK toward the prodrug ganciclovir.
- University of Illinois at Chicago United States
- Max Planck Society Germany
- Max Planck Institute for Multidisciplinary Sciences Germany
Binding Sites, Molecular Sequence Data, Herpesvirus 1, Human, Thymidine Kinase, Protein Structure, Tertiary, Adenosine Diphosphate, Adenosine Triphosphate, Structural Biology, Amino Acid Sequence, Phosphorylation, Nucleoside-Phosphate Kinase, Molecular Biology, Herpesvirus 4, Equid
Binding Sites, Molecular Sequence Data, Herpesvirus 1, Human, Thymidine Kinase, Protein Structure, Tertiary, Adenosine Diphosphate, Adenosine Triphosphate, Structural Biology, Amino Acid Sequence, Phosphorylation, Nucleoside-Phosphate Kinase, Molecular Biology, Herpesvirus 4, Equid
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