Structure of vaccinia virus thymidine kinase in complex with dTTP: insights for drug design.

ABSTRACT:

Background

Development of countermeasures to bioterrorist threats such as those posed by the smallpox virus (variola), include vaccination and drug development. Selective activation of nucleoside analogues by virus-encoded thymidine (dThd) kinases (TK) represents one of the most successful strategies for antiviral chemotherapy as demonstrated for anti-herpes drugs. Vaccinia virus TK is a close orthologue of variola TK but also shares a relatively high sequence identity to human type 2 TK (hTK), thus achieving drug selectivity relative to the host enzyme is challenging.

Results

In order to identify any differences compared to hTK that may be exploitable in drug design, we have determined the crystal structure of VVTK, in complex with thymidine 5'-triphosphate (dTTP). Although

SUBMITTER: El Omari K 

PROVIDER: S-EPMC1636055 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature