1ki6

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spinqualitylabelsall models 1ki6, resolution 2.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE I COMPLEXED WITH A 5-IODOURACIL ANHYDROHEXITOL NUCLEOSIDE

Overview

Antiherpes therapies are principally targeted at viral thymidine kinases, and utilize nucleoside analogs, the triphosphates of which are inhibitors, of viral DNA polymerase or result in toxic effects when incorporated into, DNA. The most frequently used drug, aciclovir (Zovirax), is a relatively, poor substrate for thymidine kinase and high-resolution structural, information on drugs and other molecules binding to the target is, therefore important for the design of novel and more potent chemotherapy, both in antiherpes treatment and in gene therapy systems where thymidine, kinase is expressed. Here, we report for the first time the binary, complexes of HSV-1 thymidine kinase (TK) with the drug molecules aciclovir, and penciclovir, determined by X-ray crystallography at 2.37 A resolution., Moreover, from new data at 2.14 A resolution, the refined structure of the, complex of TK with its substrate deoxythymidine (R = 0.209 for 96% of all, data) now reveals much detail concerning substrate and solvent, interactions with the enzyme. Structures of the complexes of TK with four, halogen-containing substrate analogs have also been solved, to resolutions, better than 2.4 A. The various TK inhibitors broadly fall into three, groups which together probe the space of the enzyme active site in a, manner that no one molecule does alone, so giving a composite picture of, active site interactions that can be exploited in the design of novel, compounds.

About this Structure

1KI6 is a Protein complex structure of sequences from Human herpesvirus 4 with SO4 and AHU as ligands. Active as Thymidine kinase, with EC number 2.7.1.21 Full crystallographic information is available from OCA.

Reference

Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands., Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR, Proteins. 1998 Aug 15;32(3):350-61. PMID:9715911

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