Z-DNA binding proteins as targets for structure-based virtual screening.
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 the 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 as 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.
Kim
Doyoun
D
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
Lee
Young-Ho
YH
Hwang
Hye-Yeon
HY
Kim
Kyeong Kyu
KK
Park
Hyun-Ju
HJ
D000818:Animals; D017076:Computer-Aided Design; D043542:DNA, Z-Form / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000503:physiopathology; D007239:Infections / Q000188:drug therapy / Q000382:microbiology; D011485:Protein Binding
D043542:DNA, Z-Form; D004268:DNA-Binding Proteins