3VTK

THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE 1 IN COMPLEX WITH ADP AND 5-IODO-DEOXYURIDINE-MONOPHOSPHATE

Summary for 3VTK

• Entry DOI: 10.2210/pdb3vtk/pdb
• Descriptor: THYMIDINE KINASE, ADENOSINE-5'-DIPHOSPHATE, 5-IODO-2'-DEOXYURIDINE-5'-MONOPHOSPHATE, ... (4 entities in total)
• Functional Keywords: key enzyme in thymidine salvage pathway, additional thymidylate kinase activity, target for anti-herpes viral drugs, transferase
• Biological source: Herpes simplex virus (type 1 / strain F)
• Total number of polymer chains: 1
• Total formula weight: 38066.88

Authors

Wild, K.,Schulz, G.E. (deposition date: 1997-04-01, release date: 1997-10-22, Last modification date: 2024-02-28)

Primary citation

Wild, K.,Bohner, T.,Folkers, G.,Schulz, G.E.
The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue.
Protein Sci., 6:2097-2106, 1997

PubMed Abstract: 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.

PubMed: 9336833

Experimental method

X-RAY DIFFRACTION (3 Å)