2VTK: Thymidine Kinase From Herpes Simplex Virus Type 1 In Complex With Adp And Deoxythymidine

Thymidine kinase from Herpes simplex virus type 1 (TK) was crystallized in an N-terminally truncated but fully active form. The structures of TK complexed with ADP at the ATP-site and deoxythymidine-5'-monophosphate (dTMP), deoxythymidine (dT), or idoxuridine-5'-phosphate (5-iodo-dUMP) at the substrate-site were refined to 2.75 A, 2.8 A, and 3.0 A resolution, respectively. TK catalyzes the phosphorylation of dT resulting in an ester, and the phosphorylation of dTMP giving rise to an anhydride. The presented TK structures indicate that there are only small differences between these two modes of action. Glu83 serves as a general base in the ester reaction. Arg163 parks at an internal aspartate during ester formation and binds the alpha-phosphate of dTMP during anhydride formation. The bound deoxythymidine leaves a 35 A3 cavity at position 5 of the base and two sequestered water molecules at position 2. Cavity and water molecules reduce the substrate specificity to such an extent that TK can phosphorylate various substrate analogues useful in pharmaceutical applications. TK is structurally homologous to the well-known nucleoside monophosphate kinases but contains large additional peptide segments.
PDB ID: 2VTKDownload
MMDB ID: 58253
PDB Deposition Date: 1997/4/1
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2VTK: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 2VTK
Label Count Molecule
Proteins (2 molecules)
Thymidine Kinase
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

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