CRYSTAL-STRUCTURES OF THE THYMIDINE KINASE FROM HERPES-SIMPLEX VIRUS TYPE-I IN COMPLEX WITH DEOXYTHYMIDINE AND GANCICLOVIR

The crystal structures of thymidine kinase from herpes simplex virus t ype-1 complexed with its natural substrate deoxythymidine (dT) and com plexed with the guanosine analogue Ganciclovir have been solved. Both structures are in the C222(1) crystal form with two molecules per asym metric unit related by a noncrystallographic two-fold axis. The presen t models have been refined to 2.8 Angstrom and 2.2 Angstrom, with crys tallographic R factors of 24.1% and 23.3% for the dT and Ganciclovir c omplexes respectively, without the inclusion of any solvent molecules. The core of the molecule exhibits high structural homology with adeny late kinase and other nucleotide binding proteins. These structural si milarities provide an insight into the mechanism of nucleoside phospho rylation by thymidine kinase.