Z-DNA Binding Proteins as Targets for Structure-Based Virtual Screening

Author(s): Doyoun Kim, Young -Ho Lee, Hye-Yeon Hwang, Kyeong Kyu Kim, Hyun-Ju Park

Journal Name: Current Drug Targets

Volume 11 , Issue 3 , 2010


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Abstract:

Z-DNA, the alternative form of double-stranded DNA involved in a variety of nucleotide metabolism, is recognized and stabilized by specific Z-DNA binding proteins (ZBPs). Three ZBPs known in vertebrates --ADAR1, DAI and PKZ-- modulate innate immunity, particularly, the IFN-induced immune response. The E3L protein of vaccinia virus appears to compete with the host ZBP for Z-DNA binding, thereby suppressing the host immune system. ZBPs are, therefore, considered to be attractive therapeutic targets for infectious and immune diseases. Recent advances in computer-aided drug development combined with the high-resolution crystal and NMR structures of ZBPs have enabled us to discover novel candidates for ZBP inhibitors. In this study, we present an overview of Z-DNA and known ZBPs as drug targets, and summarize recent progress in the structure-based identification of ZBP inhibitors.

Keywords: Z-DNA, Z-DNA binding protein, ADAR1, DAI (DLM-1/ZBP1), PKZ, E3L, Zα domain, Zβ domain, computeraided drug design, virtual screening

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Article Details

VOLUME: 11
ISSUE: 3
Year: 2010
Page: [335 - 344]
Pages: 10
DOI: 10.2174/138945010790711905
Price: $65

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