Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy.

ABSTRACT: Unlike most DNA viruses, poxviruses replicate in the cytoplasm of host cells. They encode enzymes needed for genome replication and transcription, including their own thymidine and thymidylate kinases. Some herpes viruses encode only 1 enzyme catalyzing both reactions, a peculiarity used for prodrug activation to obtain maximum specificity. We have solved the crystal structures of vaccinia virus thymidylate kinase bound to TDP or brivudin monophosphate. Although the viral and human enzymes have similar sequences (42% identity), they differ in their homodimeric association and active-site geometry. The vaccinia TMP kinase dimer arrangement is orthogonal and not antiparallel as in human enzyme. This different monomer orientation is related to the presence of a canal connecting the edge of th

SUBMITTER: Caillat C 

PROVIDER: S-EPMC2579350 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature