期刊
DRUG DISCOVERY TODAY
卷 27, 期 3, 页码 759-776出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2021.12.001
关键词
Tubulin; Colchicine-binding-site inhibitors; X-ray crystallography
资金
- US National Institutes of Health (NIH) [1R01CA148706]
- US Department of Defense [W81XWH2010011]
- U.S. Department of Defense (DOD) [W81XWH2010011] Funding Source: U.S. Department of Defense (DOD)
This review summarizes the crystal structures of tubulin in complexes with various CBSIs, aiming to facilitate the discovery of new generations of tubulin inhibitors.
Tubulin is an important cancer drug target. Compounds that bind at the colchicine site in tubulin have attracted significant interest as they are generally less affected by multidrug resistance than other potential drugs. Modeling is useful in understanding the interactions between tubulin and colchicine binding site inhibitors (CBSIs), but because the colchicine binding site contains two flexible loops whose conformations are highly ligand-dependent, modeling has its limitations. X-ray crystallography provides experimental pictures of tubulin-ligand interactions at this challenging colchicine site. Since 2004, when the first X-ray structure of tubulin in complex with N-deacetyl-N-(2-mercaptoacetyl)-colchicine (DAMA-colchicine) was published, many X-ray crystal structures have been reported for tubulin complexes involving the colchicine binding site. In this review, we summarize the crystal structures of tubulin in complexes with various CBSIs, aiming to facilitate the discovery of new generations of tubulin inhibitors.
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