1VTK

THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE 1 IN COMPLEX WITH ADP AND DEOXYTHYMIDINE-MONOPHOSPHATE

1VTK の概要

• エントリーDOI: 10.2210/pdb1vtk/pdb
• 分子名称: THYMIDINE KINASE, ADENOSINE-5'-DIPHOSPHATE, THYMIDINE-5'-PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: key enzyme in thymidine salvage pathway, additional thymidylate kinase activity, target for anti-herpes viral drugs, transferase
• 由来する生物種: Herpes simplex virus (type 1 / strain F)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37955.01

構造登録者

Wild, K.,Schulz, G.E. (登録日: 1997-04-01, 公開日: 1997-10-22, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.75 Å)