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Computer-aided active-site-directed modeling of the Herpes Simplex Virus 1 and human thymidine kinase by Gerd Folkers; Susanne Trumpp-Kallmeyer; Oliver Gutbrod; Sabine Krickl; Jürgen Fetzer; Günther M. Keil is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Computer-aided active-site-directed modeling of the Herpes Simplex Virus 1 and human thymidine kinase about?

Thymidine kinase (TK), which is induced by Herpes Simplex Virus 1 (HSV1), plays a key role in the antiviral activity of guanine derivatives such as aciclovir (ACV). In contrast, ACV shows only low affinity to the corresponding host cell enzyme. In order to define the differences in substrate binding of the two enzymes on molecular level, models for the three-dimensional (3-D) structures of the active sites of HSV1-TK and human TK were developed. The reconstruction of the active sites started from primary and secondary structure analysis of various kinases. The results were validated to homologous enzymes with known 3-D structures. The models predict that both enzymes consist of a central core L3-sheet structure, connected by loops and c~-helices very similar to the overall structure of other nucleotide binding enzymes. The phosphate binding site is made up of a highly conserved glycine-rich loop at the N-terminus of the proteins and a conserved region at the C-terminus. The thymidine recognition site was found about 100 amino acids downstream from the phosphate binding loop. The differing substrate specificity of human and HSV1-TK can be explained by amino-acid substitutions in the

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Author

Gerd Folkers; Susanne Trumpp-Kallmeyer; Oliver Gutbrod; Sabine Krickl; Jürgen Fetzer; Günther M. Keil

Publisher

Springer Netherlands; Springer-Verlag; Kluwer Academic Publishers; Springer Science and Business Media LLC (ISSN 0920-654X)

Published

1991

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Physical Sciences)