|
KMID : 0370220090530040222
|
|
Yakhak Hoeji
2009 Volume.53 No. 4 p.222 ~ p.227
|
|
|
Docking Studies of Camptothecin Analogues into Human Topoisomerase I-DNA Complex
|
|
Park In-Seon
Kim Bo-Yeon
Kim Choon-Mi
Choi Sun
|
|
|
Abstract
|
|
|
|
Human topoisomerase I (Topo I) plays a pivotal role in cell replication, transcription and repair and, therefore, is an important anti-cancer target. 20S-camptothecin (CPT) is a representative Topo I inhibitor. Compounds belonging to CPT family inhibit the religation step of Topo I-DNA by binding to the DNA cleavage site. Computational docking studies with Surflex-Dock were carried out to investigate the binding modes between Topo I-DNA binary complex structure and the ligand such as 20S-CPT and 9,10-substituted 20S-CPT analogues. The docking results demonstrated that most of the compounds with value under intercalated exactly between the -1 and +1 DNA bases, deeply toward the cleavage site. The complex was stabilized by hydrogen-bonding and hydrophobic interactions with both the enzyme and the DNA. The compounds with value above were poorly docked and did not intercalate. In addition, the docking results confirmed the overall correlation between the values and docking scores, indicating the possible use of the modeling for the prediction of biological activity and design of potential inhibitors.
|
|
|
KEYWORD
|
|
|
topoisomerase I-DNA complex, camptothecin, docking, binding modes
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|