title: Structure to 1.9 A 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.
abstract: Treatment of herpes infections with nucleoside analogues requires as an initial step the activation of the compounds by thymidine kinase. As an aid to developing more effective chemotherapy, both for treatment of recurrent herpes infection and in gene therapy systems where thymidine kinase is expressed, two high-resolution X-ray structures of thymidine kinase have been compared: one with the relatively poor substrate aciclovir (Zovirax), the other with a synthetic inhibitor having an N2-substituted guanine. Both compounds have similar binding modes in spite of their size difference and apparently distinct ligand properties.
authors.affiliation: Division of Biomedical Sciences, Randall Institute, King's College, London, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Bennett
authors.forename: F
authors.initials: F
authors.lastname: Wien
authors.forename: J N
authors.initials: JN
authors.lastname: Champness
authors.forename: T
authors.initials: T
authors.lastname: Batuwangala
authors.forename: T
authors.initials: T
authors.lastname: Rutherford
authors.forename: W C
authors.initials: WC
authors.lastname: Summers
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Wright
authors.forename: M R
authors.initials: MR
authors.lastname: Sanderson
mesh_terms: D000212:Acyclovir / Q000378:metabolism; D018360:Crystallography, X-Ray; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism