Structure to 1.9 angstrom resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir

Treatment of herpes infections with nucleoside analogues requires as an ini tial step the activation of the compounds by thymidine kinase. As an aid to developing more effective chemotherapy, both for treatment of recurrent he rpes infection and in gene therapy systems where thymidine kinase is expres sed, two high-resolution X-ray structures of thymidine kinase have been com pared: one,vith the relatively poor substrate aciclovir (Zovirax), the othe r with a synthetic inhibitor having an N-2-substituted guanine, Both compou nds have similar binding modes in spite of their size difference and appare ntly distinct ligand properties. (C) 1999 Federation of European Biochemica l Societies.